Galphaq and Galpha11 proteins mediate endothelin-1 signaling in neural crest-derived pharyngeal arch mesenchyme.
Endothelin-A (ET(A)) 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(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 Galpha(q)/Galpha(11)-null mice die around E11.0, whereas Galpha(q)((-/-))Galpha(11)((+/-)) mice survive to birth with hypomorphic phenotypes similar to, but less severe than, ET(A) or ET-1-null mice. To determine whether ET-1 signaling is transduced by Galpha(q)/Galpha(11) proteins, we examined the expression patterns of several ET-1 dependent and independent transcription factors in Galpha(q)/Galpha(11)-deficient embryos. Expression of genes encoding the ET-1-dependent transcription factors Dlx3, Dlx6, dHAND, and eHAND was specifically downregulated in the pharyngeal arches of Galpha(q)/Galpha(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 Galpha(q) and Galpha(11) proteins serve as the intracellular mediators of ET-1 signaling in the pharyngeal arch mesenchyme.
Ivey
Kathryn
K
Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, , Dallas, TX 75390-9104, USA.
Tyson
Brandi
B
Ukidwe
Pallavi
P
McFadden
David G
DG
Levi
Giovanni
G
Olson
Eric N
EN
Srivastava
Deepak
D
Wilkie
Thomas M
TM
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001934:Branchial Region / Q000196:embryology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D019332:Endothelin-1 / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D018507:Gene Expression Regulation, Developmental; D020962:Heterotrimeric GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics; D017403:In Situ Hybridization; D051957:MSX1 Transcription Factor; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D029961:Zebrafish Proteins
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D019332:Endothelin-1; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D014157:Transcription Factors; D029961:Zebrafish Proteins; C088334:Distal-less homeobox proteins; C100597:Dlx6 protein, mouse; C095572:Hand1 protein, mouse; C498766:Hand2 protein, mouse; C410915:hand2 protein, zebrafish; C097341:helix-loop-helix protein, eHAND