The Gq/11 family of Gα subunits is necessary and sufficient for lower jaw development

Kanai, S. M.; Garcia, C. R.; Augustus, M. R.; Sharafeldeen, S. A.; Brooks, E. P.; Sucharov, J.; Lencer, E. S.; Nichols, J. T.; Clouthier, D. E.

doi:10.1101/2024.09.17.611698

bioRxiv · 10.1101/2024.09.17.611698

The Gq/11 family of Gα subunits is necessary and sufficient for lower jaw development

Kanai, S. M.·Garcia, C. R.·Augustus, M. R.·Sharafeldeen, S. A.·Brooks, E. P.·Sucharov, J.·Lencer, E. S.·Nichols, J. T.·Clouthier, D. E.

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Abstract

Vertebrate jaw development is coordinated by highly conserved ligand-receptor systems such as the peptide ligand Endothelin 1 (Edn1) and Endothelin receptor type A (Ednra), which are required for patterning of lower jaw structures. The Edn1/Ednra signaling pathway establishes the identity of lower jaw progenitor cells by regulating expression of numerous patterning genes, but the intracellular signaling mechanisms linking receptor activation to gene regulation remain poorly understood. As a first step towards elucidating this mechanism, we examined the function of the Gq/11 family of G subunits in zebrafish using pharmacological inhibition and genetic ablation of Gq/11 activity and transgenic induction of a constitutively active Gq protein in edn1-/- embryos. Genetic loss of Gq/11 activity fully recapitulated the edn1-/- phenotype, with genes encoding G11 being most essential. Furthermore, inducing Gq activity in edn1-/-embryos not only restored Edn1/Ednra-dependent jaw structures and gene expression signatures but also caused homeosis of the upper jaw structure into a lower jaw-like structure. These results indicate that Gq/11 is necessary and sufficient to mediate the lower jaw patterning mechanism for Ednra in zebrafish. Summary statementGq/11 is the signaling mediator downstream of Endothelin 1 and Endothelin Receptor Type A that drives tissue patterning for all lower jaw structures in zebrafish.

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Kanai, S. M., Garcia, C. R., Augustus, M. R., Sharafeldeen, S. A., Brooks, E. P., Sucharov, J., Lencer, E. S., Nichols, J. T., Clouthier, D. E.. 2024-09-19. The Gq/11 family of Gα subunits is necessary and sufficient for lower jaw development. https://doi.org/10.1101/2024.09.17.611698

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