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