Endothelin-A (ETA) is a G-protein-coupled receptor expressed in the neural crest-derived mesenchyme of the pharyngeal arches during craniofacial development. Targeted deletion of the ETA receptor or its ligand endothelin-1 (ET-1) causes cleft palate and hypoplasia of the mandible, otic cup, and tympanic ring. Previously we showed that Gαq/Gα11-null mice die around E11.0, whereas Gαq(-/-)Gα11(+/-) mice survive to birth with hypomorphic phenotypes similar to, but less severe than, ETA or ET-1-null mice. To determine whether ET-1 signaling is transduced by Gαq/Gα11 proteins, we examined the expression patterns of several ET-1 dependent and independent transcription factors in Gαq/Gα11-deficient embryos. Expression of genes encoding the ET-1-dependent transcription factors Dl×3, Dl×6, dHAND, and eHAND was specifically downregulated in the pharyngeal arches of Gαq/Gα11-deficient mice. In contrast, pharyngeal arch expression of the homeobox gene Msx1, which is not regulated by ET-1 signaling, was maintained in these embryos. We conclude that the Gαq and Gα11 proteins serve as the intracellular mediators of ET-1 signaling in the pharyngeal arch mesenchyme. © 2003 Elsevier Science (USA). All rights reserved.
Ivey, K., Tyson, B., Ukidwe, P., McFadden, D. G., Levi, G., Olson, E. N., … Wilkie, T. M. (2003). Gαq and Gα11 proteins mediate endothelin-1 signaling in neural crest-derived pharyngeal arch mesenchyme. Developmental Biology, 255(2), 230–237. https://doi.org/10.1016/S0012-1606(02)00097-0