PUBLICATION
The Gq/11 family of Gα subunits is necessary and sufficient for lower jaw development
- Authors
- 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.
- ID
- ZDB-PUB-250402-8
- Date
- 2025
- Source
- Development (Cambridge, England) : (Journal)
- Registered Authors
- Keywords
- CRISPR/Cas9, Craniofacial development, Heterotrimeric G protein, Single cell RNA-sequencing, Small molecule inhibitor, Zebrafish
- Datasets
- GEO:GSE275013
- MeSH Terms
-
- Jaw*/embryology
- Jaw*/metabolism
- GTP-Binding Protein alpha Subunits*/metabolism
- Animals, Genetically Modified
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- GTP-Binding Protein alpha Subunits, Gq-G11*/genetics
- GTP-Binding Protein alpha Subunits, Gq-G11*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Animals
- Receptor, Endothelin A/genetics
- Receptor, Endothelin A/metabolism
- Endothelin-1/genetics
- Endothelin-1/metabolism
- Body Patterning/genetics
- Signal Transduction
- Gene Expression Regulation, Developmental
- PubMed
- 40171762 Full text @ Development
Citation
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. (2025) The Gq/11 family of Gα subunits is necessary and sufficient for lower jaw development. Development (Cambridge, England). :.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping