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

Development of the vertebrate jaw apparatus depends on highly conserved signaling pathways. Patterning of the lower jaw is driven by Endothelin receptor type A (Ednra) and secreted ligand Endothelin 1 (Edn1). The Ednra signaling pathway establishes the identity of lower jaw progenitors by regulating expression of numerous patterning genes, but the intracellular signaling mechanisms linking receptor activation to gene regulation remains poorly understood. As a first step towards addressing this question, we examined the function of the Gq/11 family of Gα subunits in zebrafish using pharmacological and genetic ablation of Gq/11 activity and transgenic induction of a constitutively active Gq protein in edn1-/- embryos. Loss of Gq/11 activity fully recapitulated the edn1-/- phenotype, with genes encoding for G11 being most essential. Furthermore, inducing Gq activity in edn1-/- embryos not only restored Ednra-dependent jaw structures and gene expression signatures but also caused homeosis of the upper jaw structures 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. Zebrafish embryos were first treated with YM-254890 or DMSO (control) between 16 - 36 hours post fertilization (hpf). Then, cranial neural crest cells (NCCs) labeled with two transgenes, sox10:mRFP and fli1a:EGFP, were isolated at 36 hpf by fluorescence activated cell sorting (FACS). Isolated cranial NCCs were then analyzed by scRNA-seq.