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(-/-)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.
Original language | English (US) |
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Pages (from-to) | 230-237 |
Number of pages | 8 |
Journal | Developmental Biology |
Volume | 255 |
Issue number | 2 |
DOIs | |
State | Published - 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