q and Gα11 proteins mediate endothelin-1 signaling in neural crest-derived pharyngeal arch mesenchyme

Kathryn Ivey, Brandi Tyson, Pallavi Ukidwe, David G. McFadden, Giovanni Levi, Eric N. Olson, Deepak Srivastava, Thomas M. Wilkie

Research output: Contribution to journalArticle

46 Scopus citations

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 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(-/-)11(+/-) 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.

Original languageEnglish (US)
Pages (from-to)230-237
Number of pages8
JournalDevelopmental Biology
Volume255
Issue number2
DOIs
StatePublished - Mar 15 2003

Keywords

  • Craniofacial development
  • DHAND/HAND2
  • Dl×3
  • Dl×6
  • EHAND/HAND1
  • Endothelin
  • G-protein
  • Gα/Gα
  • Neural crest
  • Pharyngeal arches

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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