Exacerbated sonic hedgehog signalling promotes a transition from chemical pre-patterning of chicken reticulate scales to mechanical skin folding

Many examples of self-organized embryonic patterning can be attributed to chemically mediated systems comprising interacting morphogens. However, mechanical patterning also contributes to the emergence of biological forms. For example, various studies have demonstrated that diverse patterns arise fr...

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Main Authors: Rory L. Cooper, Ebrahim Jahanbakhsh, Gabriel N. Santos Durán, Michel C. Milinkovitch
Format: Article
Language:English
Published: The Royal Society 2025-04-01
Series:Open Biology
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Online Access:https://royalsocietypublishing.org/doi/10.1098/rsob.240342
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author Rory L. Cooper
Ebrahim Jahanbakhsh
Gabriel N. Santos Durán
Michel C. Milinkovitch
author_facet Rory L. Cooper
Ebrahim Jahanbakhsh
Gabriel N. Santos Durán
Michel C. Milinkovitch
author_sort Rory L. Cooper
collection DOAJ
description Many examples of self-organized embryonic patterning can be attributed to chemically mediated systems comprising interacting morphogens. However, mechanical patterning also contributes to the emergence of biological forms. For example, various studies have demonstrated that diverse patterns arise from elastic instabilities associated with the constrained growth of soft materials, which generate wrinkles, creases and folds. Here, we show that between days 12 and 13 of in ovo development, transient experimentally increased activity of the sonic hedgehog pathway in the chicken embryo, through a single intravenous injection of smoothened agonist (SAG), abolishes the Turing-like chemical patterning of reticulate scales on the ventral footpad and promotes a transition to mechanical labyrinthine skin folding. Using in situ hybridization, nanoindentation and labelling of proliferating cells, we confirm that skin surface folding is associated with the loss of signalling placode pre-patterning as well as increased epidermal growth and stiffness. Using additional in ovo hydrocortisone treatments, we also demonstrate that experimentally induced hyper-keratinization of the skin mechanically restricts SAG-induced folding. Finally, we verify our experimental findings with mechanical growth simulations built from volumetric light sheet fluorescence microscopy data. Overall, we reveal that pharmacological perturbation of the underlying gene regulatory network can abolish chemical skin appendage patterning and replace it with self-organized mechanical folding.
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spelling doaj-art-df3c22e90608474d8bcb81ff9e4cfcd82025-08-20T02:27:32ZengThe Royal SocietyOpen Biology2046-24412025-04-0115410.1098/rsob.240342Exacerbated sonic hedgehog signalling promotes a transition from chemical pre-patterning of chicken reticulate scales to mechanical skin foldingRory L. Cooper0Ebrahim Jahanbakhsh1Gabriel N. Santos Durán2Michel C. Milinkovitch3Genetics and Evolution, University of Geneva, Geneva, SwitzerlandGenetics and Evolution, University of Geneva, Geneva, SwitzerlandGenetics and Evolution, University of Geneva, Geneva, SwitzerlandGenetics and Evolution, University of Geneva, Geneva, SwitzerlandMany examples of self-organized embryonic patterning can be attributed to chemically mediated systems comprising interacting morphogens. However, mechanical patterning also contributes to the emergence of biological forms. For example, various studies have demonstrated that diverse patterns arise from elastic instabilities associated with the constrained growth of soft materials, which generate wrinkles, creases and folds. Here, we show that between days 12 and 13 of in ovo development, transient experimentally increased activity of the sonic hedgehog pathway in the chicken embryo, through a single intravenous injection of smoothened agonist (SAG), abolishes the Turing-like chemical patterning of reticulate scales on the ventral footpad and promotes a transition to mechanical labyrinthine skin folding. Using in situ hybridization, nanoindentation and labelling of proliferating cells, we confirm that skin surface folding is associated with the loss of signalling placode pre-patterning as well as increased epidermal growth and stiffness. Using additional in ovo hydrocortisone treatments, we also demonstrate that experimentally induced hyper-keratinization of the skin mechanically restricts SAG-induced folding. Finally, we verify our experimental findings with mechanical growth simulations built from volumetric light sheet fluorescence microscopy data. Overall, we reveal that pharmacological perturbation of the underlying gene regulatory network can abolish chemical skin appendage patterning and replace it with self-organized mechanical folding.https://royalsocietypublishing.org/doi/10.1098/rsob.240342elastic instabilitiesself-organizationskin appendageschickenreticulate scalesphysics of biology
spellingShingle Rory L. Cooper
Ebrahim Jahanbakhsh
Gabriel N. Santos Durán
Michel C. Milinkovitch
Exacerbated sonic hedgehog signalling promotes a transition from chemical pre-patterning of chicken reticulate scales to mechanical skin folding
Open Biology
elastic instabilities
self-organization
skin appendages
chicken
reticulate scales
physics of biology
title Exacerbated sonic hedgehog signalling promotes a transition from chemical pre-patterning of chicken reticulate scales to mechanical skin folding
title_full Exacerbated sonic hedgehog signalling promotes a transition from chemical pre-patterning of chicken reticulate scales to mechanical skin folding
title_fullStr Exacerbated sonic hedgehog signalling promotes a transition from chemical pre-patterning of chicken reticulate scales to mechanical skin folding
title_full_unstemmed Exacerbated sonic hedgehog signalling promotes a transition from chemical pre-patterning of chicken reticulate scales to mechanical skin folding
title_short Exacerbated sonic hedgehog signalling promotes a transition from chemical pre-patterning of chicken reticulate scales to mechanical skin folding
title_sort exacerbated sonic hedgehog signalling promotes a transition from chemical pre patterning of chicken reticulate scales to mechanical skin folding
topic elastic instabilities
self-organization
skin appendages
chicken
reticulate scales
physics of biology
url https://royalsocietypublishing.org/doi/10.1098/rsob.240342
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