Galphaq and Galpha11 proteins mediate endothelin-1 signaling in neural crest-derived pharyngeal arch mesenchyme

Dev Biol. 2003 Mar 15;255(2):230-7. doi: 10.1016/s0012-1606(02)00097-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Branchial Region / embryology
  • Branchial Region / metabolism*
  • DNA-Binding Proteins / genetics
  • Endothelin-1 / metabolism*
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Gene Expression Regulation, Developmental
  • Heterotrimeric GTP-Binding Proteins / deficiency
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Homeodomain Proteins / genetics
  • In Situ Hybridization
  • MSX1 Transcription Factor
  • Mesoderm / metabolism
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Neural Crest / embryology
  • Neural Crest / metabolism*
  • Phenotype
  • Signal Transduction
  • Transcription Factors / genetics
  • Zebrafish Proteins


  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Distal-less homeobox proteins
  • Dlx6 protein, mouse
  • Endothelin-1
  • Hand1 protein, mouse
  • Hand2 protein, mouse
  • Homeodomain Proteins
  • MSX1 Transcription Factor
  • Transcription Factors
  • Zebrafish Proteins
  • hand2 protein, zebrafish
  • helix-loop-helix protein, eHAND
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Heterotrimeric GTP-Binding Proteins