Neural crest cells are among the most remarkable cells in the vertebrate embryo. Originating at the dorsal edge of the closing neural tube, they undergo an epithelial-to-mesenchymal transition, delaminate from the tube, and migrate along defined pathways to colonize distant targets. Once there, they differentiate into an astonishing range of structures: the bones and cartilage of the face, portions of the heart including the outflow tract, the peripheral nervous system and its enteric division in the gut, and the pigment-producing melanocytes of the skin. Because this single lineage feeds so many organ systems, a perturbation to neural crest development could, in principle, produce developmental phenotypes that appear scattered across the body but share one upstream cause.

The review, authored by Lijia Ju, Beibei Niu, Zexin Zhang, Tianyi Cui, Yining Liu, Meirong Yang, Lingdong Zhu, and Bo Pan, affiliated with the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College and the Children’s Hospital Affiliated to Shandong University, traces the full exposure pathway. Maternal uptake of micro- and nanoplastics occurs through ingestion and inhalation, and the particles have demonstrated the ability to cross biological barriers, including the maternal-fetal interface. The authors then evaluate how such particles might perturb neural crest cells both directly and indirectly, assembling evidence from chick embryo studies, whole-embryo models, organoids, and maternal-exposure experiments.

The direct mechanisms are detailed and mechanistically coherent. Particles that contact or are taken up by neural crest cells may disrupt lysosomal and autophagic function, the cellular recycling system that keeps organelles healthy. Mitochondrial injury follows, reducing adenosine triphosphate production and elevating reactive oxygen species, the chemically reactive molecules that damage DNA, proteins, and membranes. Oxidative stress in turn activates stress signaling pathways such as mitogen-activated protein kinase cascades, while particles can also interfere with cytoskeletal remodeling, the dynamic reorganization of the cell’s internal scaffold that migrating cells depend upon. The downstream consequences include impaired cell survival, failed delamination from the neural tube, deficient migration, and poor colonization of target sites such as the pharyngeal arches that give rise to craniofacial structures.

The indirect mechanisms are equally important and often overlooked. Macrophages, the immune cells that patrol the maternal-fetal interface and embryonic tissues, readily engulf particles. Once loaded with plastic, these macrophages may undergo immunometabolic reprogramming, altering the inflammatory signals, chemotactic cues, and extracellular-matrix composition that guide neural crest migration. In this scenario, the neural crest cells themselves may never internalize a particle, yet their developmental trajectory is still bent by a microenvironment that particles have changed. This distinction between direct particle uptake and indirect particle-altered signaling is central to the review’s framework and to how future experiments should be designed.

Among all the experimental systems surveyed, chick embryos currently provide the most direct evidence. In chick studies, particle-associated signals have been linked with the retention of neural crest cells in the dorsal neural tube, meaning cells that should have departed instead lingered at their origin. That retention correlated with deficient colonization of the pharyngeal arches, regional cell death, and craniofacial and cardiovascular abnormalities, phenotypes that map precisely onto the structures neural crest cells are known to build. Embryo, organoid, and maternal-exposure models contribute additional but mostly indirect evidence, involving neural tube morphogenesis, the enteric nervous system of the gut, and pigment lineages, each of which depends on neural crest or neural tube derivatives.

The authors are explicit about the limits of the current literature, and their candor is what separates this review from sensational coverage of plastic pollution. Tissue-level detection of particles does not establish that particles entered neural crest cells specifically, and an organ phenotype does not establish that the neural crest lineage was the causal target rather than a bystander. Two gaps stand out as major obstacles: human-relevant internal dosimetry, meaning measurements of what concentrations of particles actually accumulate in embryonic tissues at realistic exposure levels, and direct comparisons between neural crest cells and non-neural crest lineages within the same embryo, which would reveal whether this population is genuinely more vulnerable than its neighbors.

What the review proposes instead is a testable model. In the framework of MNP-associated environmental neurocristopathies, perturbation of neural crest development may represent a shared upstream event in a subset of cross-organ developmental phenotypes, potentially explaining why gestational exposure to micro- and nanoplastics has been associated with abnormalities in the face, heart, gut, and pigment system that otherwise seem unrelated. The authors stress that this concept should not yet be interpreted as an established causal relationship in humans. It is a hypothesis with defined experimental criteria, not a verdict.

Validation, the authors argue, will require five specific kinds of evidence. First, intact-particle localization, demonstrating with high-resolution imaging that particles physically reside within or adjacent to neural crest cells in living embryos. Second, dynamic neural crest lineage tracing, following the fate of these cells in real time rather than inferring their history from static endpoints. Third, non-neural crest controls, comparing perturbation in this lineage against other embryonic populations under identical exposure conditions. Fourth, human-relevant dose-response analysis, establishing whether the concentrations that produce effects in laboratory models overlap with the internal doses measured in human pregnancy. Fifth, mechanistic rescue experiments, in which a specific upstream defect, such as oxidative stress or autophagic failure, is corrected and the developmental phenotype is thereby prevented, which is the strongest form of causal proof available in developmental biology.

The significance of this framework extends beyond plastics. Environmental neurocristopathies as a concept, in which an environmental agent disrupts the neural crest lineage and thereby produces multi-organ developmental defects, has precedent in other toxicological contexts, and micro- and nanoplastics may represent a new and pervasive member of that category. With particles documented in placenta, amniotic fluid, umbilical cord blood, and fetal tissues, the question of whether the embryonic neural crest is exposed is no longer hypothetical; it is a matter of localization and dose. The review, published open access on 16 October 2026 and carrying the DOI 10.1186/s43591-026-00238-w, was supported by the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College and the Natural Science Foundation of Shandong Province. Its authors declare no competing interests, and its framework now awaits the experiments that will determine whether the embryonic cells that build the face, the heart, the gut, and the skin are quietly bearing the burden of the plastic age.

Subject of Research: Developmental toxicology of micro- and nanoplastics and neural crest biology

Article Title: Can exposure to micro- and nanoplastics disrupt neural crest development? Evidence and a testable model for MNP-associated environmental neurocristopathies

Article References: Can exposure to micro- and nanoplastics disrupt neural crest development? Evidence and a testable model for MNP-associated environmental neurocristopathies. (n.d.). https://doi.org/10.1186/s43591-026-00238-w

Image Credits: AI Generated

DOI: 10.1186/s43591-026-00238-w

Keywords: microplastics, nanoplastics, neural crest cells, developmental toxicology, environmental neurocristopathies, gestational exposure, maternal-fetal barrier, placenta, embryonic development, craniofacial development, oxidative stress, chick embryo model