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

TL;DR

This study shows that the Gq/11 protein family is crucial for developing the lower jaw in zebrafish, acting as a key signal in the Edn1/Ednra pathway.

Contribution

The study identifies Gq/11 as both necessary and sufficient for lower jaw development via the Edn1/Ednra signaling pathway in zebrafish.

Findings

Genetic loss of Gq/11 activity reproduces the edn1−/− jaw phenotype in zebrafish.

Inducing Gq activity in edn1−/− embryos restores lower jaw structures and gene expression.

Gq/11 activity can transform upper jaw structures into lower jaw-like structures in embryos.

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 Gα 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: Genetic and pharmacological manipulation reveal that Gq/11 is a signaling mediator acting downstream of Endothelin 1 and Endothelin Receptor Type A that drives tissue patterning for all lower jaw structures in zebrafish.

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