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Differential regulation of SHH signaling and the developmental control of species-specific jaw size through neural crest-mediated Gas1 expression

Zuzana Vavrušová, Daniel B. Chu, An Nguyen, View ORCID ProfileJennifer L. Fish, View ORCID ProfileRichard A. Schneider
doi: https://doi.org/10.1101/2021.12.17.473230
Zuzana Vavrušová
1Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA
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Daniel B. Chu
1Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA
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An Nguyen
1Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA
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Jennifer L. Fish
2Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA
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Richard A. Schneider
1Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA
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  • For correspondence: rich.schneider@ucsf.edu
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Abstract

Developmental control of jaw size is crucial to prevent disease and facilitate evolution. We have shown that species-specific differences in jaw size are established by neural crest mesenchyme (NCM), which are the jaw progenitors that migrate into the mandibular primordia. NCM relies on multiple signaling molecules including Sonic Hedgehog (SHH) to mediate interactions with mandibular epithelium that facilitate outgrowth of the jaws. SHH signaling is known to promote outgrowth and so we tested if differential regulation of the SHH pathway can account for species-specific variation in mandibular primordia size. We analyze gene expression of SHH pathway members in duck, chick, and quail, and find higher transcriptional activation in the larger mandibular primordia of duck relative to those of chick and quail. We generate quail-duck chimeras and demonstrate that such activation is NCM-mediated. Gain- and loss-of-function experiments reveal a species-specific response to SHH signaling, with the target Gas1 being most sensitive to manipulations. Gas1 overexpression and knockdown in NCM alters cell number and/or mandibular primordia size. Our work suggests that NCM-mediated changes in SHH signaling may modulate jaw size during development, disease, and evolution.

Summary Statement We have determined that Gas1, which is a component of the SHH signaling pathway, plays a key role in the development and evolution of jaw size.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 18, 2021.
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Differential regulation of SHH signaling and the developmental control of species-specific jaw size through neural crest-mediated Gas1 expression
Zuzana Vavrušová, Daniel B. Chu, An Nguyen, Jennifer L. Fish, Richard A. Schneider
bioRxiv 2021.12.17.473230; doi: https://doi.org/10.1101/2021.12.17.473230
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Differential regulation of SHH signaling and the developmental control of species-specific jaw size through neural crest-mediated Gas1 expression
Zuzana Vavrušová, Daniel B. Chu, An Nguyen, Jennifer L. Fish, Richard A. Schneider
bioRxiv 2021.12.17.473230; doi: https://doi.org/10.1101/2021.12.17.473230

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