1. G[[alpha].sub.q] and G[[alpha].sub.11] proteins mediate endothelin-1 signaling in neural crest-derived pharyngeal arch mesenchyme
- Author
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Ivey, Kathryn, Tyson, Brandi, Ukidwe, Pallavi, McFadden, David G., Levi, Giovanni, Olson, Eric N., Srivastava, Deepak, and Wilkie, Thomas M.
- Subjects
Craniology -- Research ,Endothelin -- Genetic aspects ,Endothelin -- Physiological aspects ,Developmental biology -- Research ,G proteins -- Genetic aspects ,G proteins -- Physiological aspects ,Phenotype -- Genetic aspects ,Phenotype -- Physiological aspects ,Gene expression -- Physiological aspects ,Neural crest -- Genetic aspects ,Neural crest -- Physiological aspects ,Biological sciences - Abstract
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 [ET.sub.A] 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 G[[alpha].sub.q]/G[[alpha].sub.11]-null mice die around E 11.0, whereas G[[alpha].sub.q.sup.(-/-)] G[[alpha].sub.11.sup.(+/-)] 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 G[[alpha].sub.q]/G[[alpha].sub.11] proteins, we examined the expression patterns of several ET-1 dependent and independent transcription factors in G[alpha].sub.q]/G[[alpha].sub.11]-deficient embryos. Expression of genes encoding the ET-1-dependent transcription factors D1x3, D1x6, dHAND, and eHAND was specifically downregulated in the pharyngeal arches of G[[alpha].sub.q]/G[alpha].sub.11]-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 G[[alpha].sub.q] and G[[alpha].sub.11] proteins serve as the intracellular mediators of ET-1 signaling in the pharyngeal arch mesenchyme. Keywords: G-protein; Neural crest; Pharyngeal arches; Endothelin; G[[alpha].sub.q]/G[[alpha].sub.11]; D1x3; D1x6; dHAND/HAND2; eHAND/HAND1; Craniofacial development
- Published
- 2003