In vivo sonic hedgehog pathway antagonism temporarily results in ancestral proto-feather-like structures in the chicken.
The morphological intricacies of avian feathers make them an ideal model for investigating embryonic patterning and morphogenesis. In particular, the sonic hedgehog (Shh) pathway is an important mediator of feather outgrowth and branching. However, functional in vivo evidence regarding its role duri...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-03-01
|
| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3003061 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850160951033069568 |
|---|---|
| author | Rory L Cooper Michel C Milinkovitch |
| author_facet | Rory L Cooper Michel C Milinkovitch |
| author_sort | Rory L Cooper |
| collection | DOAJ |
| description | The morphological intricacies of avian feathers make them an ideal model for investigating embryonic patterning and morphogenesis. In particular, the sonic hedgehog (Shh) pathway is an important mediator of feather outgrowth and branching. However, functional in vivo evidence regarding its role during feather development remains limited. Here, we demonstrate that an intravenous injection of sonidegib, a potent Shh pathway inhibitor, at embryonic day 9 (E9) temporarily produces striped domains (instead of spots) of Shh expression in the skin, arrests morphogenesis, and results in unbranched and non-invaginated feather buds-akin to proto-feathers-in embryos until E14. Although feather morphogenesis partially recovers, hatched treated chickens exhibit naked skin regions with perturbed follicles. Remarkably, these follicles are subsequently reactivated by seven weeks post-hatching. Our RNA-sequencing data and rescue experiment using Shh-agonism confirm that sonidegib specifically down-regulates Shh pathway activity. Overall, we provide functional evidence for the role of the Shh pathway in mediating feather morphogenesis and confirm its role in the evolutionary emergence and diversification of feathers. |
| format | Article |
| id | doaj-art-1c5a8dd9770140c996c7d60fd875073a |
| institution | OA Journals |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-1c5a8dd9770140c996c7d60fd875073a2025-08-20T02:23:00ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852025-03-01233e300306110.1371/journal.pbio.3003061In vivo sonic hedgehog pathway antagonism temporarily results in ancestral proto-feather-like structures in the chicken.Rory L CooperMichel C MilinkovitchThe morphological intricacies of avian feathers make them an ideal model for investigating embryonic patterning and morphogenesis. In particular, the sonic hedgehog (Shh) pathway is an important mediator of feather outgrowth and branching. However, functional in vivo evidence regarding its role during feather development remains limited. Here, we demonstrate that an intravenous injection of sonidegib, a potent Shh pathway inhibitor, at embryonic day 9 (E9) temporarily produces striped domains (instead of spots) of Shh expression in the skin, arrests morphogenesis, and results in unbranched and non-invaginated feather buds-akin to proto-feathers-in embryos until E14. Although feather morphogenesis partially recovers, hatched treated chickens exhibit naked skin regions with perturbed follicles. Remarkably, these follicles are subsequently reactivated by seven weeks post-hatching. Our RNA-sequencing data and rescue experiment using Shh-agonism confirm that sonidegib specifically down-regulates Shh pathway activity. Overall, we provide functional evidence for the role of the Shh pathway in mediating feather morphogenesis and confirm its role in the evolutionary emergence and diversification of feathers.https://doi.org/10.1371/journal.pbio.3003061 |
| spellingShingle | Rory L Cooper Michel C Milinkovitch In vivo sonic hedgehog pathway antagonism temporarily results in ancestral proto-feather-like structures in the chicken. PLoS Biology |
| title | In vivo sonic hedgehog pathway antagonism temporarily results in ancestral proto-feather-like structures in the chicken. |
| title_full | In vivo sonic hedgehog pathway antagonism temporarily results in ancestral proto-feather-like structures in the chicken. |
| title_fullStr | In vivo sonic hedgehog pathway antagonism temporarily results in ancestral proto-feather-like structures in the chicken. |
| title_full_unstemmed | In vivo sonic hedgehog pathway antagonism temporarily results in ancestral proto-feather-like structures in the chicken. |
| title_short | In vivo sonic hedgehog pathway antagonism temporarily results in ancestral proto-feather-like structures in the chicken. |
| title_sort | in vivo sonic hedgehog pathway antagonism temporarily results in ancestral proto feather like structures in the chicken |
| url | https://doi.org/10.1371/journal.pbio.3003061 |
| work_keys_str_mv | AT rorylcooper invivosonichedgehogpathwayantagonismtemporarilyresultsinancestralprotofeatherlikestructuresinthechicken AT michelcmilinkovitch invivosonichedgehogpathwayantagonismtemporarilyresultsinancestralprotofeatherlikestructuresinthechicken |