Inhibiting the sonic hedgehog (Shh) pathway strongly perturbs feather development in chickens by restricting feather bud outgrowth, invagination and branching, according to a study published March 20th, in the open-access journal PLOS Biology by Rory Cooper and Michel Milinkovitch from the University of Geneva, Switzerland.
Avian feathers are intricate appendages whose forms vary substantially across species and body areas, and between juvenile and adult stages. Understanding both the developmental and evolutionary mechanisms underpinning this morphological diversity has long fascinated biologists. The morphological intricacies of avian feathers make them an ideal model for investigating embryonic patterning. In particular, the Shh pathway is an important mediator of feather outgrowth and branching. However, functional in-vivo evidence regarding its role during feather development remains limited.
To fill this knowledge gap, Cooper and Milinkovitch used light sheet fluorescence microscopy imaging to study the normal patterning of embryonic feathers and how their shape develops. The authors also used precise intravenous injections of sonidegib to pharmacologically inhibit Shh pathway signaling during feather development at embryonic day 9, which precedes feather-bud outgrowth on the wings. This treatment temporarily modified Shh expression to produce striped domains instead of spots on the skin, temporarily stopped feather development, and resulted in unbranched and non-invaginated feather buds — akin to putative proto-feathers —until embryonic day 14.
Although feather development partially recovered later during development, hatched sonidegib-treated chickens exhibited naked regions of the skin surface with perturbed follicles. Remarkably, these follicles were subsequently reactivated by seven weeks post-hatching, highlighting the robustness of feather patterning as a developmental process. Overall, the study provides comprehensive functional evidence for the role of the Shh pathway in mediating feather development in chickens, supporting the idea that modified Shh signaling has contributed to the evolutionary diversification of feathers and other skin appendages such as feet scales. According to the authors, the study also demonstrates the importance of in-vivo experiments for obtaining a comprehensive understanding of developmental systems.
The authors add, "Our experiments show that while a transient disturbance in the development of feet scales can permanently turn them into feathers, it is much harder to disrupt feather development itself. The big challenge now is to understand how these genetic interactions have changed to allow for the emergence of protofeathers early in the evolution of dinosaurs."
In your coverage, please use this URL to provide access to the freely available paper in PLOS Biology: https://plos.io/3XLN4RU
Citation: Cooper RL, Milinkovitch MC (2025) In vivo sonic hedgehog pathway antagonism temporarily results in ancestral proto-featherlike structures in the chicken. PLoS Biol 23(3): e3003061. https://doi.org/10.1371/journal.pbio.3003061
Author countries: Switzerland
Funding: see manuscript
