Hox genes occupy a special place in developmental biology because their order along the chromosome mirrors the order of their expression along the head-to-tail axis of the embryo, a phenomenon known as colinearity. Genes at the posterior ends of the HoxA and HoxD clusters, including paralog groups 9 through 13, are expressed in the posterior trunk and tail regions of developing vertebrates, where they help assign identity to vertebrae, the hindgut, and the urogenital system. The new findings from zebrafish and the Iberian ribbed newt add a striking entry to this list: the same posterior Hox machinery that stamps identity onto the trunk also appears to be the trigger that first designates which cells will build the hindmost pair of appendages. This places the origin of hind appendages not at the level of morphological outgrowth, but at the level of cell fate specification, a stage that has been difficult to probe experimentally because the relevant cell populations are small, transient, and not yet visually distinct in the embryo.

The technical approach taken by the researchers reflects how modern developmental genetics has evolved to address such early events. In zebrafish, single mutations in Hox genes often produce subtle or no visible effects because of paralogy, the duplication of entire Hox clusters that occurred early in vertebrate history. Zebrafish carry duplicated Hox clusters inherited from a whole-genome duplication in the teleost lineage, meaning that a gene like hoxa9 exists in two copies, hoxa9a and hoxa9b, each capable of partially compensating for the loss of the other. Only by combining mutations across multiple paralogs — in this case five genes spanning both the HoxA and HoxD clusters — could the team reveal the full requirement for paralog group 9 and 10 function in pelvic fin formation. This combinatorial strategy mirrors what has been done in mice, where knocking out individual Hox genes rarely exposes their deepest roles, but cumulative disruption of paralog groups reveals dramatic transformations of body structure.

The complete loss of pelvic fins in zebrafish lacking these five genes is a particularly clean result because pelvic fins are the hindmost paired appendages in fish, directly analogous to hindlimbs in tetrapods. The fluorescent reporter lines used in the study allowed the researchers to visualize pelvic fin progenitor cells before any fin bud became visible under the microscope. When the five Hox genes were disrupted, these bilateral progenitor populations simply never appeared, indicating that the failure occurs at or before the stage when mesenchymal cells are first allocated to the pelvic appendage fate. This distinguishes the result from earlier work showing Hox requirements during fin or limb outgrowth and patterning, stages at which the appendage bud already exists and is growing. Here, the genes appear to act upstream of bud formation itself, at the point where a population of cells in the lateral plate mesoderm and adjacent tissue is being set aside to become the hind appendage.

The choice of the Iberian ribbed newt as a second experimental system is significant for reasons that go beyond simple taxonomic breadth. Newts belong to the salamander lineage, which is part of the lobe-finned vertebrate branch that also includes the ancestors of all tetrapods. Ray-finned fishes such as zebrafish and lobe-finned vertebrates such as newts diverged from a common ancestor more than 400 million years ago, making any shared developmental mechanism between them likely to have been present in that common ancestor. The newt experiments used CRISPR-Cas9 genome editing to disrupt all seven Hox9 and Hox10 paralogs simultaneously, a technically demanding feat in an organism with a long generation time and a large genome. The observation that animals losing hindlimbs also lost or markedly reduced expression of Prdm16, a transcription factor associated with hindlimb-forming regions, provides a molecular readout that connects the genetic disruption to a specific failure in progenitor specification rather than a general developmental defect.

Prdm16 itself is worth noting in this context. This gene encodes a chromatin-associated transcriptional regulator that has been studied primarily for its roles in adipocyte differentiation and in the development of the heart and facial structures. Its expression in prospective hindlimb-forming regions of the newt embryo, and its dependence on Hox9-10 function, suggests that it may act as a downstream effector or marker of the Hox-dependent program that establishes hind appendage progenitors. Whether Prdm16 is directly bound and regulated by Hox9-10 proteins, or whether it sits further downstream in a cascade, remains an open question that future experiments will need to address. What the current data establish is that the loss of Hox9-10 function produces a correlated loss of both the morphological appendage and a molecular marker of the appendage-forming field, strengthening the interpretation that the primary defect is in progenitor establishment.

The stepwise evolutionary model that the authors propose builds on a long history of comparative Hox biology. In insects and other protostomes, Hox genes pattern segment identity along the body axis but are not generally used to build paired appendages in the same way vertebrates deploy them. In vertebrates, the recruitment of posterior Hox genes into the appendage-patterning system has been inferred from several lines of evidence: the conserved expression of HoxA and HoxD cluster genes in developing fins and limbs across diverse species, the phenotypic consequences of Hox disruption in mice and fish, and comparative genomics showing conserved regulatory landscapes around the HoxD cluster that are active in appendages. What has been missing is direct functional evidence that the earliest step — the specification of the progenitor cells themselves — depends on posterior Hox genes, and that this dependence is shared across deeply diverged vertebrate lineages. The current study fills that gap.

The model suggests a sequence of events in the evolution of the vertebrate paired appendage system. First, an ancestral Hox9-10 program, perhaps originally functioning in trunk and tail patterning, was co-opted to designate cells for hind appendage formation. This step would have been sufficient to establish a basic posterior paired appendage. Second, additional posterior Hox genes from paralog groups 11 through 13 were incorporated into the program, expanding the patterning capacity to include proximal-distal and anterior-posterior axes within the growing appendage. Third, the expanded system was redeployed in anterior paired appendages, the pectoral fins and forelimbs, where Hox genes from paralog groups 1 through 8 also contribute to patterning in a reversed collinear fashion. This redeployment would have allowed the same core genetic machinery to build both pairs of appendages, a hallmark of the vertebrate body plan.

Supporting this model, previous comparative studies have shown that the HoxD cluster in vertebrates is flanked by regulatory elements that drive expression in developing appendages, and that these elements show signs of evolutionary conservation and modification across fish and tetrapod lineages. The HoxA cluster carries analogous regulatory landscapes. The integration of these regulatory architectures with the developmental functions now attributed to Hox9-10 in hind appendage progenitor specification provides a framework in which genetic innovation at the level of gene regulation could have progressively built the paired appendage system from simpler ancestral components.

It is important to note what the study does not claim. The authors are careful to state that their work does not directly reconstruct the evolutionary sequence of events that led to the modern paired appendage system. Developmental evidence in extant species can reveal which mechanisms are shared and therefore likely to be ancestral, but it cannot by itself demonstrate the order in which those mechanisms were assembled over deep time. Fossil evidence, paleontological records of fin and limb morphology in extinct vertebrates, and broader comparative genomic analyses will all be needed to complement the developmental data and test the stepwise model more rigorously. Nevertheless, the demonstration that Hox9-10 genes are required for hind appendage progenitor establishment in both a ray-finned fish and a lobe-finned salamander provides a strong indication that this function predates the divergence of these lineages and was likely present in the last common ancestor of jawed vertebrates.

The broader significance of this work extends into several areas of ongoing research. For developmental biologists, the identification of an early Hox-dependent step in hind appendage formation raises questions about the upstream signals that activate Hox9-10 in the relevant progenitor fields, and about the downstream targets through which Hox proteins execute their effects. For evolutionary biologists, the results provide a concrete molecular handle on the problem of how novel morphological structures arise through the modification of existing developmental programs rather than through the invention of entirely new genes. For researchers interested in regenerative biology, understanding how progenitor cells are specified for appendage formation in organisms with natural regenerative capacities, such as newts, could inform strategies for inducing regenerative responses in species that lack them.

Associate Professor Kawamura’s comments about the timeline for translating these findings into practical applications reflect a realistic assessment of where this research sits on the spectrum from basic discovery to applied science. The immediate value of the work is conceptual: it establishes a developmental connection between the posterior Hox code of the body axis and the Hox system used to build paired appendages, and it provides functional evidence for an ancestral posterior Hox program that contributed to the evolutionary assembly of the appendage-patterning system. Over the coming years, as genome editing tools become more refined and comparative developmental biology expands to include more diverse species, the principles uncovered here are likely to find relevance in studies of congenital limb malformations, in efforts to understand the genetic basis of appendage diversity across vertebrates, and in the broader quest to understand how the vertebrate body plan was assembled through evolutionary time.

The collaborative structure of the research team, drawing on expertise from Saitama University, Tottori University, the National Institute of Genetics, the National Institute for Basic Biology, and the Exploratory Research Center on Life and Living Systems, reflects the interdisciplinary nature of the questions being addressed. Genetic analysis in zebrafish requires facilities and expertise in fish husbandry, transgenesis, and imaging. CRISPR-Cas9 disruption in newts requires specialized knowledge of salamander embryology and genome editing in an organism with a genome roughly ten times the size of the human genome. Skeletal imaging, fluorescent reporter design, and comparative analysis across species each demand their own technical competencies. The integration of these approaches within a single study demonstrates how modern research into fundamental questions of body plan evolution increasingly depends on teams that span multiple institutions and multiple model systems.

As the field moves forward, several experimental directions follow naturally from this work. Identifying the direct transcriptional targets of Hox9-10 proteins in the pelvic fin progenitor field of zebrafish would help define the gene regulatory network downstream of the Hox code. Testing whether the same Hox9-10 requirement applies to pectoral fin or forelimb progenitors, or whether anterior appendages rely on a different set of Hox genes at the progenitor stage, would clarify the degree to which the ancestral program was indeed posterior-specific before being redeployed anteriorly. Extending the analysis to additional vertebrate lineages, including cartilaginous fishes and more basal ray-finned fishes, would help pinpoint when in vertebrate evolution the Hox9-10-dependent hind appendage program was established. Each of these directions builds on the foundation laid by the current study and contributes to the larger goal of understanding how one of the most consequential innovations in vertebrate history came to be.

Subject of Research: Evolutionary developmental biology of Hox genes and vertebrate paired appendages

Article Title: Ancient Hox code reveals the developmental roots of vertebrate hind fins and limbs

Article References: Ancient Hox code reveals the developmental roots of vertebrate hind fins and limbs. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: Hox genes, zebrafish, Iberian ribbed newt, pelvic fins, hindlimbs, evolutionary developmental biology, CRISPR-Cas9, PNAS, Ancient, code, reveals, developmental

The study, published in Nature Communications by Louise Perez, Lina Shi, and colleagues in the laboratory of Patricia N. Schneider, tackles one of the deepest questions in biology: how complex organs acquire genuinely new capabilities during evolution. The vertebrate eye is often cited as an example of intricate engineering, with its layered neurons, lens, and light-sensitive photoreceptors, and understanding how such a structure can be modified without breaking it is a central challenge for evolutionary developmental biology. Anableps offers an ideal natural experiment, because the species lives its life straddling two optical environments at once. Light behaves very differently in air and in water, bending to different degrees as it enters the eye and carrying different spectral information, so a retina built for underwater vision is not automatically well suited to aerial vision.

To find out what changed in the Anableps eye, the researchers turned to two of the most powerful tools in modern genomics: single-nucleus transcriptomics and spatial transcriptomics. Single-nucleus methods allow scientists to catalog which genes are switched on in thousands of individual cells, revealing the full diversity of cell types present in a tissue. Spatial transcriptomics goes a step further by mapping where those gene-expression profiles sit within the intact organ, preserving the anatomical geography that conventional sequencing destroys. Applied to the Anableps retina, these approaches produced a cell-by-cell, position-by-position atlas of gene activity, letting the team compare the dorsal half of the retina, which handles underwater light, with the ventral half, which handles aerial light.

The atlas delivered a striking first finding: the ventral retina, the region devoted to the aerial view, is developmentally expanded. In a conventional fish eye, the dorsal and ventral halves of the retina are patterned by conserved developmental signals that establish the organ’s top-bottom axis during embryogenesis. In Anableps, the team found that markers of ventral retinal identity are overrepresented, and comparative spatial profiling of developing and adult Anableps alongside the killifish, a related surface-dwelling species with an ordinary single-vision eye, showed that the boundary separating the dorsal and ventral territories has shifted toward the dorsal side. The result is a proportionally larger ventral domain. In other words, evolution did not build a new compartment in the eye; it redrew the existing map, enlarging the aerial-vision territory at the expense of the aquatic one.

The second major finding concerns the photoreceptors themselves, the cone cells that provide color vision in bright light. Cones owe their spectral sensitivity to light-absorbing proteins called opsins, and the wavelength each opsin absorbs best is determined by its amino acid sequence. Fish genomes typically harbor multiple opsin genes, or paralogs, that arose through ancient duplications, and different copies can be tuned to different parts of the light spectrum. The spatial transcriptomic data revealed that opsin expression in Anableps is regionally organized within a single cone subtype. Cones in the ventral, aerial-vision region of the retina, designated PR1 cones, express a gene called opn1mw2, whereas the corresponding cones in the dorsal, underwater region express the longer-wavelength-sensitive opn1lw paralogs.

That regional swap matters because the two optical environments demand different sensitivities. To estimate how the proteins actually perform, the researchers used machine-learning predictions of opsin spectral properties. These analyses indicated that the Opn1mw2 pigment found in the ventral cones is red-shifted relative to Opn1mw1, another member of the medium-wavelength-sensitive opsin family, but remains blue-shifted relative to the dorsal Opn1lw pigments. The ventral retina therefore occupies an intermediate spectral position: tuned differently from the dorsal retina, and presumably better matched to the quality of light arriving from above the surface, yet still drawing on the same family of cone pigments that ancestral fishes used. The adaptation is a reshuffling of existing genetic resources, not the appearance of an entirely new photoreceptor class.

Taken together, the results sketch a coherent evolutionary pathway. Anableps did not need to evolve novel genes or novel cell types to peer into the air. Instead, it co-opted the developmental machinery that already patterns the dorsal-ventral axis of the vertebrate retina, shifting the boundary between territories so that the ventral domain grew larger, and then rewired the opsin expression programs of conserved cone subtypes so that each half of the retina is tuned to its own light environment. This kind of remodeling, in which ancient developmental circuits are redeployed to produce new proportions and new regional specializations, is increasingly recognized as a common route to evolutionary novelty, particularly in organs as complex and constrained as the eye.

The study also highlights how non-model organisms can illuminate questions that laboratory staples cannot. Anableps is not a traditional genetic model like the zebrafish or the mouse, but its unusual lifestyle makes it uniquely informative about sensory adaptation. By pairing modern transcriptomic techniques with careful comparisons against a related fish with conventional vision, the researchers could distinguish what is genuinely unusual about the Anableps retina from what is shared across teleosts. The finding that dorsal-ventral patterning markers reveal an expanded ventral identity, corroborated by the spatial comparison with killifish at both developmental and adult stages, gives the conclusion a firm anatomical footing rather than resting on gene-expression differences alone.

For the four-eyed fish itself, the payoff is a life lived at the interface. Cruising the surface with half of each eye in each world, Anableps can scan for insects and predators in the air while simultaneously watching for threats and prey below, a capability that depends on a retina partitioned into two spectrally and developmentally distinct zones. The new work shows that this partition is written into the organ’s developmental blueprint and into the pigment choices of its cone cells. It is a vivid reminder that evolution is often a tinkerer rather than an inventor, achieving dramatic functional change by enlarging, shifting, and reprogramming the parts it already has.

The research, funded by start-up funds from Louisiana State University and a grant from the National Science Foundation’s Integrative Organismal Systems program, was published as an open-access article, making the full dataset and methods available to other teams studying retinal evolution and sensory ecology. As spatial and single-cell technologies continue to spread beyond traditional model species, eyes like those of Anableps are likely to yield further secrets about how vertebrate sensory organs adapt to the world’s many light environments, one developmental tweak at a time.

Subject of Research: Evolutionary remodeling of the ventral retina enabling simultaneous aerial and aquatic vision in the four-eyed fish Anableps anableps

Article Title: Evolutionary remodeling of the ventral retina enables aerial vision in the four-eyed fish Anableps anableps

Article References: Perez, L., Shi, L., Daspit, A., Pruett, K. N., Smith, C., Prideaux, A., Sousa, J. F., & Schneider, P. N. (2026). Evolutionary remodeling of the ventral retina enables aerial vision in the four-eyed fish Anableps anableps. Nature Communications. https://doi.org/10.1038/s41467-026-78775-4

Image Credits: AI Generated

DOI: 10.1038/s41467-026-78775-4

Keywords: four-eyed fish, Anableps anableps, retina, evolutionary developmental biology, opsins, spatial transcriptomics, single-nucleus transcriptomics, photoreceptors, aerial vision, dorsal-ventral patterning, non-model organisms, Nature Communications

Technau joined the journal as Co-Editor-in-Chief in 2014, succeeding Diethard Tautz, and for more than a decade led the journal alongside Jürgen Heinze. Following Heinze’s departure at the end of 2024, Stollewerk joined as Co-Editor-in-Chief in January 2025, and the two worked together until Technau’s departure this summer. That handover sequence matters for continuity, because editorial leadership transitions at society-owned journals are often the moments when scope, standards and community relationships either drift or consolidate. The editorial frames Technau’s tenure as a period of stability for the journal’s scientific quality and its deliberately broad zoological remit, a claim that carries weight given how fragmented the discipline has become over the same period.

The fragmentation is worth unpacking, because it explains why the journal’s next move is significant rather than merely administrative. Zoology today is not a single field but a federation of them: molecular evolution, developmental biology, physiology, morphology, behaviour, ecology, systematics, evolutionary biology and biodiversity science all study animals, yet they often publish in disjointed venues, use different methods, and speak different technical languages. A journal that claims to span that range needs editors who can evaluate work far outside their own specialisation, or an editorial board whose collective expertise covers the entire territory. Technau’s own research program illustrates the kind of integrative perspective the journal has prized. Working with cnidarians, the group that includes corals, jellyfish and sea anemones, he investigates the origin and evolution of animal body plans, using genomic, molecular and developmental approaches to probe fundamental features of animal organisation such as germ layers and nervous systems. Cnidarians occupy a pivotal position on the animal tree, sitting outside the bilaterians, which makes them powerful models for asking which aspects of animal development were present in the common ancestor of all animals and which arose later. That expertise in molecular evolution and evolutionary developmental biology, the editorial notes, has been particularly valuable for a journal dedicated to integrating the many disciplines of modern zoology.

Beyond manuscript-level judgement, the editorial highlights a less visible but arguably more consequential part of the job: building the editorial board itself. The quality of a journal’s peer review depends heavily on whether its Associate Editors collectively cover the field’s diversity, and on whether those editors are drawn from the international community rather than a narrow network. Technau is credited with identifying and recruiting Associate Editors from different areas of zoology and from around the world, cultivating the close exchange between Editors-in-Chief and Associate Editors that shapes a journal’s scientific profile while tying it to the wider research community. Stollewerk also offers a personal note of thanks, describing the collaboration since her arrival in January 2025 as marked by thoughtful judgement and a willingness to discuss both individual manuscripts and broader editorial questions, which she credits with easing her own transition into the role. On behalf of the journal, its Editorial Board and the DZG, she extends warm thanks for his twelve years of commitment.

The incoming Co-Editor-in-Chief brings a complementary profile. Stefan Richter’s research spans morphology, systematics, phylogenetics and evolutionary biology, with a particular focus on understanding organismal diversity and evolutionary relationships. Where Technau’s work reached down to the genomic and developmental basis of body-plan features, Richter’s tradition reaches across the comparative anatomy and phylogenetic reconstruction that have long anchored zoological classification. He also arrives with substantial editorial experience from a number of journals in zoology, systematics and evolutionary biology, which should shorten the learning curve that typically accompanies a handover of this kind. In practical terms, the pairing suggests the journal intends to keep one foot in molecular and developmental zoology and the other in organismal and comparative biology, the two poles between which much of the discipline’s integration problem lies.

Richter’s connection to the journal’s founding society is unusually direct. He served on the Executive Board of the German Zoological Society for many years and was the DZG’s President in 2017 and 2018. The editorial argues that his appointment comes at an especially appropriate time, because Frontiers in Zoology is currently strengthening the integration between the journal and the society that founded it. That relationship is not cosmetic. Society journals live or die by their standing within their disciplinary communities, and the DZG’s subdiscipline groups represent precisely the network of specialists a broad-scope journal needs to draw upon for review, section leadership and agenda-setting.

The concrete expression of that integration is a new editorial structure now being introduced. The expertise of the Editorial Board is being organised into the major subdisciplines of zoology, and authors will be able to submit their work directly to the section most appropriate for their research. Members of the DZG’s corresponding subdiscipline groups have joined the journal as Section Editors and will help develop these sections, further strengthening the connection between the international Editorial Board and the scientific community represented by the society. For authors, the immediate effect is navigational: rather than a single undifferentiated stream of submissions, papers on, say, neurobiology, systematics or behavioural ecology will enter through dedicated channels staffed by editors from those communities. That can shorten the distance between a submission and an editor who genuinely understands the field, improve the matching of reviewers, and signal to readers that the journal’s scope is not nominal but actively curated.

The editorial is careful to frame the reform as an affirmation of an old principle rather than a departure from it. Since its foundation, the journal has operated on the premise that zoology gains its strength from the diversity of its disciplines and from bringing together different approaches to understanding animals, from molecules, development and physiology to morphology, behaviour, ecology, evolution, systematics and biodiversity. The new sections are intended to make that breadth more visible while maintaining the high standards of scientific quality that remain at the heart of the journal. In other words, the structural change is presented as a visibility problem solved: the breadth already existed in the board’s expertise, and the sections simply expose it.

The timing also reflects broader pressures on scientific publishing. Journals across the life sciences are competing for submissions in an environment where preprints, megajournals and specialised outlets all pull at authors’ loyalties, and where society journals must demonstrate added value beyond a brand name. Direct-to-section submission is one of the mechanisms journals use to differentiate themselves, because it promises faster, better-informed editorial triage. For a journal owned by a national zoological society and published open access under a Creative Commons Attribution licence, the calculation is clear: the more visibly the journal maps onto the society’s own disciplinary structure, the more it becomes the natural home for that community’s output, and the more the society’s members have a stake in its success.

What happens next will be watched by authors in organismal biology, a community that has watched several broad-scope zoology venues narrow or reposition over the past decade. The editorial closes with a double gesture that captures the moment: a welcome to Richter and a commitment to work with the Editorial Board, the DZG and the journal’s authors to develop the journal and promote excellent research across the full breadth of zoology, alongside a renewed thanks to Technau for twelve years of dedicated service and best wishes for his future. Leadership changes at journals rarely make headlines, but in a discipline as sprawling as zoology, who sits in the editor’s chair, and how the editorial machinery is organised beneath them, shapes which questions get published, which communities feel at home, and ultimately which strands of animal science stay connected to one another. Frontiers in Zoology has bet that the answer lies in formalising its breadth, one section at a time.

Subject of Research: Editorial leadership transition and new section-based editorial structure at the journal Frontiers in Zoology

Article Title: Continuity and new perspectives at Frontiers in Zoology

Article References: Stollewerk, A. (2026). Continuity and new perspectives at Frontiers in Zoology. Frontiers in Zoology, 23(1), Article 36. https://doi.org/10.1186/s12983-026-00636-z

Image Credits: AI Generated

DOI: 10.1186/s12983-026-00636-z

Keywords: Frontiers in Zoology, zoology, editorial leadership, German Zoological Society, Stefan Richter, Ulrich Technau, evolutionary developmental biology, systematics, open access publishing, editorial board, phylogenetics, scientific journals

The research, led by Xinyang Fan, Wei Zhu, Jing Zhou and colleagues at Yunnan Agricultural University, together with Lihua Qiu of Kunming University, set out to answer a deceptively simple question: what, at the level of gene expression, distinguishes the skin of a feathered foot from that of a scaled one? The team took advantage of a natural feature of Wuding chickens, in which some individuals display feathered feet and others scaled feet, providing an internally controlled comparison within a single breed. This design minimizes the genetic background noise that often complicates comparisons across divergent breeds and allows researchers to focus on the molecular differences that track the trait itself.

The investigators focused on embryonic day 12, a critical window in avian skin development when the fate of skin appendages is being actively specified. At this stage, the embryonic shank is making decisions: will it produce feather follicles, with their complex down-growing architecture, or will it settle into the simpler, plate-like scale program? By sequencing the RNA transcripts present in shank skin from feathered-foot and scaled-foot embryos, the researchers could catalogue every gene whose activity differed between the two skin types, capturing the molecular conversation underway as the two tissues diverge.

The scale of the transcriptional divergence was substantial. The team identified 1,119 differentially expressed genes between feathered and scaled shank skin, a molecular signature indicating that the two tissues are following genuinely distinct developmental trajectories rather than differing by a single switch. When the researchers subjected this gene set to functional enrichment analysis, the results converged on pathways long known to orchestrate feather follicle development: the Wnt/β-catenin cascade, the bone morphogenetic protein, or BMP, pathway, and the Hedgehog signaling system. These pathways are the canonical architects of skin appendage patterning across vertebrates, and their prominence in the feathered-foot transcriptome suggested that the trait is built from conserved developmental machinery redeployed in an unusual location.

To move from a list of candidate genes to an understanding of regulatory architecture, the authors constructed a protein–protein interaction network from their differentially expressed genes. Such networks map the functional relationships among gene products, and nodes with unusually high connectivity often mark hub genes that coordinate the activity of many downstream targets. In this analysis, one gene stood out: Sonic hedgehog, universally abbreviated SHH. This gene encodes a secreted signaling protein that acts as a morphogen, a molecule that diffuses through tissue and instructs cells to adopt different fates depending on the concentration they experience. SHH is famous in developmental biology for its roles in limb patterning, neural tube organization and, crucially, in the epithelial–mesenchymal crosstalk that drives feather and hair follicle formation.

Identifying SHH as a hub was a correlation; the next step was to test whether it could actually cause the cellular changes associated with feathered-foot development. The researchers turned to an in vitro system using dermal fibroblasts, the connective tissue cells of the dermis that form the structural foundation of the feather follicle and provide the inductive signals that pattern the overlying epidermis. Working with fibroblasts isolated at embryonic day 7, an earlier stage than the sequencing time point, the team manipulated SHH expression directly, either forcing the cells to produce excess SHH or silencing the gene with RNA interference. This paired overexpression and knockdown strategy allowed the researchers to observe what happens when the candidate regulator is turned up or down, respectively.

The results were clear and bidirectional. When SHH was overexpressed, the fibroblasts activated the canonical Wnt/β-catenin pathway, a signaling route in which β-catenin protein accumulates in the cell nucleus and switches on genes that promote growth and organogenesis. Alongside this pathway activation, the cells proliferated significantly faster and progressed more vigorously through the cell cycle. The knockdown experiments produced the mirror image: reducing SHH suppressed both Wnt/β-catenin activity and cell proliferation. Because feather follicle morphogenesis depends on rapid, coordinated expansion of the dermal cell population, these findings suggest that SHH helps create the cellular conditions that feather formation requires.

The study went deeper into the mechanisms by which SHH boosts fibroblast growth. The team found that SHH promoted proliferation through the activation of two additional signaling axes, JAK2/STAT3 and AKT/mTOR, both of which are well-characterized growth-promoting pathways that relay signals from the cell surface to the machinery of cell division and metabolism. SHH also appeared to delay cellular senescence, the state of permanent growth arrest that cells enter under stress, by modulating the expression of P53, P21 and SIRT1, a trio of regulators that sit at the heart of the senescence program. Finally, SHH inhibited programmed cell death, or apoptosis, apparently by elevating the ratio of the anti-apoptotic protein BCL2 to the pro-apoptotic protein BAX and suppressing Caspase-3, an executioner enzyme of the apoptotic cascade. Together, these effects paint SHH as a master switch that pushes dermal fibroblasts into a pro-growth, anti-death, anti-aging state.

The authors interpret these findings as evidence that dermal SHH establishes a microenvironment favorable to feather follicle development, potentially through coordinated activation of the Wnt/β-catenin pathway. In this model, the difference between a feathered and a scaled foot is not merely the presence or absence of a follicle-inducing signal in the epidermis, but also whether the underlying dermis is in a proliferative, permissive state that can support follicle outgrowth. By keeping fibroblasts dividing, warding off senescence and preventing apoptosis, SHH would ensure that the dermal compartment has the cellular capacity to build and sustain the elaborate structure of a feather follicle, allowing the feather program to take hold on a body region that normally develops scales.

Beyond its relevance to poultry, the work speaks to a broader question in evolutionary developmental biology: how do novel structures arise from old genetic parts? The feathered foot is a classic example of ectopic expression, in which a trait characteristic of one body region, the wing, appears in another, the leg. Studies in other breeds, notably the Peking duck-footed and Brahmas-type chickens, have implicated shifts in developmental pathways in this transformation, and the present study adds SHH and its downstream proliferative program to the growing list of molecular players. Because the Wuding chicken provides a within-breed comparison, the findings are particularly clean, and they suggest that modulating the timing, location or intensity of a conserved morphogen like SHH can be enough to redirect an entire skin appendage program. The research, supported by the Major Science and Technology Projects of Yunnan Province and approved by the Animal Care and Use Committee of Yunnan Agricultural University, was published open access on 28 September 2026 in BMC Genomics under the corresponding authorship of Yongwang Miao. As genomic tools continue to illuminate the developmental genetics of domestic animals, traits once treated as mere curiosities of fancy poultry are proving to be powerful windows into the fundamental rules that shape the diversity of life.

Subject of Research: Molecular regulation of feathered-foot morphogenesis in Wuding chickens via dermal SHH and Wnt/β-catenin signaling

Article Title: Transcriptomic and functional analysis reveals dermal SHH potentially regulates feathered-foot morphogenesis in Wuding chickens through the Wnt/β-catenin pathway

Article References: Fan, X., Zhu, W., Zhou, J., Liu, L., Wang, W., Qiu, L., & Miao, Y. (2026). Transcriptomic and functional analysis reveals dermal SHH potentially regulates feathered-foot morphogenesis in Wuding chickens through the Wnt/β-catenin pathway. BMC Genomics. https://doi.org/10.1186/s12864-026-13397-0

Image Credits: AI Generated

DOI: 10.1186/s12864-026-13397-0

Keywords: Wuding chicken, feathered foot, Sonic hedgehog, SHH, Wnt/β-catenin signaling, dermal fibroblast, feather follicle development, transcriptomics, RNA sequencing, embryonic development, skin appendage, evolutionary developmental biology

The research team focused on two intertwined biological systems: the thyroid gland, the endocrine engine that drives amphibian metamorphosis, and the skin, the organ that must ultimately protect a frog from the drying hazards of terrestrial life. In most familiar frogs, such as the African clawed frog Xenopus laevis, development follows an aquatic indirect pathway: eggs hatch into free-swimming, feeding tadpoles that live in water for weeks or months before a dramatic hormonal surge transforms them into air-breathing, land-capable adults. In contrast, A. villiersi practices what biologists call terrestrial indirect development. Its larvae are endotrophic, meaning they rely entirely on internal yolk reserves rather than feeding, and they metamorphose while still enclosed within the protective jelly of the nest. This lifestyle raises a fundamental question in evolutionary developmental biology: when a lineage shifts its reproduction onto land, do the underlying developmental programs of its organs get rebuilt from scratch, or do they simply run on a slightly adjusted schedule?

To find out, the researchers carried out detailed histological analyses of froglets and larvae across the entire developmental period, examining thin tissue sections under the microscope to track the maturation of the thyroid gland and the step-by-step remodeling of the skin. The thyroid gland is central to the story because in all anurans studied to date, the hormones it produces, chiefly thyroxine and triiodothyronine, orchestrate the sweeping anatomical changes of metamorphosis, from the regression of the tail to the reconstruction of the gut and the maturation of the limbs. Understanding when the thyroid first becomes active, and how its secretory tissue expands over time, therefore provides a hormonal timetable against which every other developmental event can be measured.

The results showed that the sequence of thyroid maturation in the moss frog is conserved, meaning it follows essentially the same ordered progression seen both in classical aquatic indirect developers such as Xenopus and in terrestrial direct developers that skip the tadpole stage entirely. The gland forms, differentiates its hormone-producing follicular cells, and ramps up activity on a schedule that mirrors what has been documented across the frog family tree. This conservation is significant because it suggests that the endocrine control system for metamorphosis is deeply entrenched in anuran biology. Even when an evolutionary transition moves the whole process out of water and into a jelly capsule on land, the hormonal machinery itself does not need to be reinvented.

The skin, however, tells a more nuanced tale. In its earliest stages, the skin of the moss frog tadpole recapitulates features that are typical of free-living aquatic larvae. The young epidermis consists of only two cell layers, and it is studded with unicellular glands, single secretory cells embedded in the surface layer. Most remarkably, the larval skin carries neuromasts, the sensory organs of the lateral line system that fishes and aquatic amphibians use to detect water movements. The presence of these water-sensing organs in a tadpole that never leaves its jelly nest is a vivid example of developmental inertia: the larval program builds the structures it would need for aquatic life, even when that life is spent in a droplet of moisture on a mossy bank.

As metamorphosis proceeds, the skin undergoes the full suite of rearrangements familiar from other frogs. The two-layered larval epidermis is replaced by a three-layered adult epidermis, and a tough outer layer called the stratum corneum forms, providing the keratinized barrier that is essential for surviving exposure to air. The simple unicellular glands are supplanted by multicellular mucus glands, which keep the skin moist, and granular glands, which in many frog species store defensive toxins or antimicrobial compounds. Beneath the surface, the pigment-bearing cells known as melanophores are reorganized into new layers, completing the transition from a larval skin designed for an aquatic existence to an adult skin engineered for terrestrial conditions. In other words, despite the radically different ecological context in which this metamorphosis unfolds, the skin still passes through the same larval architecture and the same adult remodeling as that of a pond-dwelling tadpole.

The timing of these events also revealed telling correlations. The neuromasts appear at hatching, differentiate into functional sensory organs, and then degenerate shortly before the completion of metamorphosis, a schedule that tracks closely with the maturation of the thyroid gland. This coupling makes sense from a physiological standpoint: as thyroid hormone levels rise to drive the adult transformation, larval-specific structures that are no longer needed are systematically eliminated, a process biologists call apoptosis or programmed cell death. The synchronized disappearance of the lateral line organs as the thyroid reaches maturity is a textbook example of how a single hormonal signal can coordinate the simultaneous remodeling of multiple organ systems.

Yet the study did detect subtle differences in timing when the moss frog was compared with aquatic indirect developers using heterochrony plots, graphical tools that map the onset and sequence of developmental events across species. Two shifts stood out. The development of dermal melanophores, the pigment cells embedded in the skin’s connective tissue layer, is pre-displaced, meaning it begins earlier in development than in aquatic tadpoles. Conversely, the formation of multicellular granular glands is post-displaced, occurring later than expected. These are minor adjustments rather than wholesale rewiring, but they hint at how evolution fine-tunes developmental timing to suit new ecological circumstances. An earlier investment in skin pigmentation might be advantageous for an animal developing on land, where protection from ultraviolet radiation and background matching could matter from the moment of hatching, while a delayed deployment of granular glands could reflect the different defensive pressures of a terrestrial jelly nest compared with predator-rich pond water.

Perhaps the most conceptually important finding is what the researchers did not find. Despite the minor timing shifts, there was no evidence of temporal co-dissociation, the phenomenon in which different components of an organ system drift apart in their developmental schedules over evolutionary time. The skin’s various elements, from its epidermal layers to its glands to its pigment cells, all developed in a tightly integrated fashion, leading the authors to describe the skin as an integrated unit of evolution. This modularity has broad implications for how scientists understand morphological evolution. If the skin develops as a coordinated package, then evolutionary changes affecting one component tend to drag the others along, and major life-history transitions, such as the move from aquatic to terrestrial reproduction, can be achieved without fragmenting or fundamentally reorganizing the developmental pathways that build the organ.

Taken together, the study delivers a clear message about the mechanics of evolutionary change in amphibians. The transition to terrestrial life histories in frogs, one of the most ecologically significant shifts in the group’s history, does not require a fundamental overhaul of skin development or thyroid function. Instead, the ancient metamorphic program, governed by a conserved endocrine timetable, can be compressed into a jelly nest on a wet mountainside and still produce a fully functional, land-ready frog. The de Villiers moss frog, by retaining tadpole-typical features such as lateral line organs and unicellular glands even as it completes its development on land, offers a living snapshot of how evolutionary innovation often works not by inventing new biology, but by rescheduling and repurposing the old. As amphibians worldwide face mounting pressures from habitat loss and climate change, understanding the developmental flexibility that allowed some lineages to escape the water may prove more than an academic curiosity; it is a window into the deep reserves of evolvability that have carried frogs through hundreds of millions of years of environmental change.

Subject of Research: Thyroid gland maturation and skin metamorphosis in the terrestrial indirect-developing de Villiers moss frog

Article Title: Temporal patterns of thyroid gland maturation and skin metamorphosis in terrestrial indirect-developing de Villiers moss frogs (Arthroleptella villiersi Hewitt, 1935)

Article References: Naumann, B., Schweiger, S., & Müller, H. (2026). Temporal patterns of thyroid gland maturation and skin metamorphosis in terrestrial indirect-developing de Villiers moss frogs (Arthroleptella villiersi Hewitt, 1935). Frontiers in Zoology. https://doi.org/10.1186/s12983-026-00631-4

Image Credits: AI Generated

DOI: 10.1186/s12983-026-00631-4

Keywords: Arthroleptella villiersi, anuran metamorphosis, thyroid gland, skin development, heterochrony, terrestrialization, evolutionary developmental biology, tadpole, epidermis, lateral line, Frontiers in Zoology, amphibian life history

The central paradox the authors confront is chemical. ROS—including superoxide, hydrogen peroxide and hydroxyl radicals—are inherently reactive, which is precisely why uncontrolled ROS production is toxic. Yet evolution has exploited this very reactivity. Hydrogen peroxide, in particular, is small, electrically neutral and membrane-permeable, allowing it to diffuse rapidly through tissue and act as a broadcast signal. At wound margins, ROS can oxidize the cysteine residues of target proteins, reversibly altering the activity of phosphatases, kinases and transcription factors. In this way, a transient oxidative pulse functions as a second-messenger system, converting the physical fact of injury into a coordinated genetic and cellular response. The review frames this as oxidative eustress—beneficial, regulated stress—as opposed to the destructive oxidative distress associated with pathology.

What makes the new synthesis compelling is its comparative breadth. The authors assemble evidence spanning the metazoan tree, from cnidarians such as Hydra and Nematostella, which can rebuild entire bodies from small fragments, to planarian flatworms, annelids, echinoderms, fish, amphibians and mammals. In nearly every regenerative model examined, pharmacological or genetic suppression of ROS production—most often by blocking the NADPH oxidase enzymes, or NOXes, that generate superoxide at the wound—impairs regeneration. Conversely, exogenous hydrogen peroxide can, in some systems, partially rescue defective regenerative responses. The consistency of this pattern across such distantly related animals raises the tantalizing possibility that ROS signaling is not a collection of independent evolutionary accidents but a deeply rooted, possibly ancestral, component of the regeneration program.

The review is careful, however, to emphasize that conserved does not mean uniform. The regulatory roles and modes of action of ROS vary considerably among species, tissues and regenerative contexts. In some animals, ROS act primarily in the earliest wound-healing phase, recruiting immune cells and initiating proliferation; in others, oxidative signals persist into blastema formation, the mass of progenitor cells from which the new structure grows. The downstream targets differ as well: ROS have been implicated in activating Wnt, FGF, ERK and JNK signaling pathways, in modulating apoptosis, and in shaping the extracellular matrix, but the specific wiring differs from one organism to the next. This variability, the authors argue, is precisely why continued comparative study is essential. Only by mapping ROS involvement across many species can researchers distinguish genuinely common mechanisms from species-specific embellishments.

This comparative logic carries the review into deeper evolutionary waters. The evolutionary history of regeneration remains one of the great unresolved puzzles in biology. Why can a salamander regrow an entire limb while a mouse cannot? Why do some annelids regenerate their whole posterior body axis while closely related species fail at the same task? Two competing frameworks dominate the field: regeneration as an ancestral capacity repeatedly lost in lineages that traded it for other advantages, or regeneration as a trait independently gained, assembled from pre-existing wound-healing and developmental machinery. The authors argue that ROS data can inform this debate. If ROS signaling sits at the base of regenerative responses across the animal tree, it may represent an ancient, conserved layer of the process—one that lineages with poor regenerative abilities have not necessarily lost, but perhaps fail to deploy correctly.

That reframing has direct therapeutic implications, and it is here that the review makes its most forward-looking argument. Humans regenerate well in the liver, moderately in skin and bone, and hardly at all in the heart, spinal cord and limbs. If ROS signaling is a conserved trigger of regenerative programs, then modulating redox state could offer a lever to reactivate latent regenerative capacity in poorly regenerating human tissues. The concept is not fanciful. Studies in zebrafish and axolotl have shown that adjusting ROS levels can influence heart regeneration and appendage regrowth, and redox-sensitive pathways such as ERK and Wnt are already major targets of regenerative medicine research. The review suggests that a rigorous understanding of when, where and at what concentration ROS act could enable precisely timed redox interventions—boosting regeneration without tipping tissues into the oxidative damage that fuels fibrosis, inflammation and cancer.

The authors are equally candid about the obstacles. ROS are fleeting, highly reactive and difficult to measure with spatial and temporal precision, and many of the tools used to manipulate them—broad-spectrum antioxidants, generic NOX inhibitors—are blunt instruments with off-target effects. To address this, the review includes a supplementary compendium of the functional tools available to modulate ROS production in regeneration studies, cataloguing the main pharmacological inhibitors and activators as well as the principal targets for RNA interference, morpholino and knockout approaches. Standardizing and refining this toolkit, the authors contend, is a prerequisite for the field’s maturation. Without it, discrepancies between studies may reflect technical artifacts rather than genuine biological differences, muddying the comparative analyses on which evolutionary conclusions depend.

The review also identifies major knowledge gaps that will shape the next decade of work. The precise molecular targets of ROS during regeneration remain incompletely defined in most models; the dose, duration and gradients of oxidative signals at wounds are poorly quantified; and the interplay between ROS and other injury-induced signals—calcium fluxes, bioelectric gradients, mechanical forces and immune-derived cytokines—is only beginning to be explored. Another open question is whether ROS participate in the establishment of positional memory, the information that tells a regenerating blastema whether to build a hand, a tail or a head. Answering these questions will require combining live redox biosensors, genetic models and comparative approaches across species that span the breadth of regenerative ability, from master regenerators to refractory ones.

What emerges from the synthesis is a view of regeneration as a redox-gated process whose ancient logic may still be latent within our own cells. The authors, based at institutions including Université Paris Cité, Université Côte d’Azur, the University of Manchester, Sorbonne Université and École Normale Supérieure, argue that studying ROS across metazoan diversity serves a dual purpose: it illuminates how regeneration evolved, and it reveals why some species, including our own, regenerate poorly. Both lines of inquiry converge on the same practical prize—new strategies in regenerative medicine grounded in evolutionary insight rather than trial and error. If the oxidizing burst that follows injury truly is a conserved call to rebuild, then learning to read, and perhaps to amplify, that ancient signal could one day help human tissues do what salamanders have done for millions of years: grow back.

Subject of Research: The role of reactive oxygen species signaling in animal regeneration and its evolutionary and therapeutic implications

Article Title: Understanding ROS signaling and evolution during animal regeneration offers promising opportunities for novel therapeutic approaches

Article References: Vullien, A., John, J., Rampon, C., Amaya, E., Röttinger, E., & Gazave, E. (2026). Understanding ROS signaling and evolution during animal regeneration offers promising opportunities for novel therapeutic approaches. Cellular and Molecular Life Sciences. https://doi.org/10.1007/s00018-026-06392-x

Image Credits: AI Generated

DOI: 10.1007/s00018-026-06392-x

Keywords: reactive oxygen species, ROS signaling, regeneration, regenerative medicine, oxidative eustress, NADPH oxidase, evolutionary developmental biology, blastema, wound healing, redox biology, hydrogen peroxide, comparative biology

Published in the prestigious Proceedings of the National Academy of Sciences, this groundbreaking work advances a novel conceptual framework centered on “shared competence” — the ability of two distinct embryonic cell lineages to give rise to analogous adult structures. The research zeroes in on the little skate (Leucoraja erinacea), a cartilaginous fish whose paired fins and gill arches serve as model serial homologs, structures repeated along the body that share evolutionary and developmental origins.

Traditionally, serial homology—where one body part repeats or transforms into another—has been viewed through the lens of gradual evolutionary transformations. For instance, insect wings are believed to have evolved through modifications of leg segments, an idea supported by recent genetic and developmental insights. Similarly, 19th-century biologist Karl Gegenbauer proposed that the paired appendages of jawed vertebrates might have originated via transformation of gill arches, the bony supports of fish gills. However, defining serial homology precisely has remained elusive due to the complex interplay between anatomy, genetics, and development.

One perplexing aspect has been the embryonic origin of these structures. Gill arches are generally known to derive from the neural crest, a multipotent embryonic cell population famous for its versatility. In contrast, paired fins and limbs arise from the lateral plate mesoderm, a separate germ layer. This dichotomy raises the question: How can structures emanating from such distinct origins exhibit serial homology?

A pivotal insight emerged from a 2020 study led by Gillis’s former postdoc Victoria Sleight, which utilized advanced fate-mapping techniques to examine the early skate embryo’s cellular composition. They discovered that rather than a strict boundary between neural crest and lateral plate mesoderm, there exists significant cellular intermingling at the head-trunk boundary. This blending creates a mesenchymal field composed of cells from both germ layers, collectively competent to generate either gill arches or paired fins.

The latest experimental investigations, conducted by University of Chicago PhD candidate Michael Wen under co-advisors Gillis and Victoria Prince, rigorously tested the functional equivalence of these embryonic populations. Wen performed precise cell transplantation experiments, moving neural crest-derived cells intended for gill arch formation into developing fin fields, and reciprocally transplanting mesodermal cells into gill arch territories. Remarkably, transplanted cells integrated seamlessly and contributed normally to the new skeletal environment.

This interchangeability means that despite their differing embryonic origins, the cells share intrinsic developmental “competence.” They respond similarly to local signaling cues, allowing them to build serially homologous structures with comparable cartilage architectures. Essentially, the environmental context guides cell fate more decisively than their embryonic heritage.

This shared competence model reframes the understanding of serial homology by shifting emphasis from historical morphological transformations to contemporary cellular developmental potentials. It suggests that homologous repeating structures may arise not solely through evolutionary modification of one structure into another, but through the evolutionary conservation of cellular responsiveness within overlapping developmental fields.

Complex genomic regulatory landscapes likely underlie this phenomenon. Wen hypothesizes that the genomic architecture governing neural crest and lateral plate mesoderm cells shares key elements enabling their reciprocal plasticity. Future research is poised to dissect these gene regulatory networks to elucidate the molecular basis of shared competence.

While these findings deepen the developmental narrative, the evolutionary origin question of paired fins remains incompletely resolved, mainly because of gaps in the fossil record. Unlike the well-documented fin-to-limb transition, evidence for how paired fins themselves emerged is sparse, limiting direct paleontological corroboration of these developmental insights.

Nevertheless, Gillis and collaborators emphasize the broader applicability of their findings. If similar principles hold true across various vertebrate structures—such as vertebrae or digits in mammals—it could revolutionize how biologists conceptualize serial homology and morphological evolution.

The study also exemplifies the power of integrative approaches combining embryology, genetics, and experimental manipulations to address enduring evolutionary questions. It highlights the little skate as a valuable non-traditional model organism for uncovering cellular and molecular dynamics inaccessible in classical systems.

Outside of this focal inquiry, Gillis’s lab has begun expanding into other spheres of developmental biology, though this line of research yielded numerous foundational discoveries and conceptual frameworks that will undoubtedly influence future studies across evolutionary developmental biology.

Supporting this research were prominent funding sources including the National Science Foundation and the Owens Family Foundation, along with institutional fellowships from the University of Chicago and the Marine Biological Laboratory. These grants underscore the vital role of sustained investment in basic science discoveries.

To visualize these concepts, detailed skeletal preparations of little skate hatchlings exhibit the intricate arrangements of cartilage and mineralization within paired fins and gill arches, affirming the anatomical relevance of the shared competence principle. Fluorescent imaging of early embryos reveals the overlapping germ layer contributions, providing a vivid developmental context for these findings.

In sum, this innovative research upends traditional views by revealing an unexpected developmental equivalence between neural crest and mesodermal cell populations that undergird serially homologous structures. This paradigm opens new avenues to unravel how complex morphological patterns are repeated and evolved throughout vertebrate history, framing serial homology in terms of developmental plasticity and genomic regulation rather than mere evolutionary transformations.

Subject of Research: Animals

Article Title: Shared competence forms the basis of gill arch and paired fin serial homology

News Publication Date: 16-Mar-2026

Web References:
https://www.pnas.org/doi/10.1073/pnas.2529365123

References:
M.T.C. Wen, V.E. Prince, & J.A. Gillis (2026). Shared competence forms the basis of gill arch and paired fin serial homology. Proceedings of the National Academy of Sciences of the United States of America. DOI: 10.1073/pnas.2529365123

Image Credits:
Andrew Gillis, Marine Biological Laboratory (MBL); Michael Wen, University of Chicago/MBL

Keywords:
Developmental biology, serial homology, paired fins, gill arches, neural crest, lateral plate mesoderm, little skate, evolutionary biology, embryonic cells, morphogenesis, gene regulation