These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Signaling pathways crucial for craniofacial development revealed by endothelin-A receptor-deficient mice.
    Author: Clouthier DE, Williams SC, Yanagisawa H, Wieduwilt M, Richardson JA, Yanagisawa M.
    Journal: Dev Biol; 2000 Jan 01; 217(1):10-24. PubMed ID: 10625532.
    Abstract:
    Most of the bone and cartilage in the craniofacial region is derived from cephalic neural crest cells, which undergo three primary developmental events: migration from the rhombomeric neuroectoderm to the pharyngeal arches, proliferation as the ectomesenchyme within the arches, and differentiation into terminal structures. Interactions between the ectomesenchymal cells and surrounding cells are required in these processes, in which defects can lead to craniofacial malformation. We have previously shown that the G-protein-coupled endothelin-A receptor (ET(A)) is expressed in the neural crest-derived ectomesenchyme, whereas the cognate ligand for ET(A), endothelin-1 (ET-1), is expressed in arch epithelium and the paraxial mesoderm-derived arch core; absence of either ET(A) or ET-1 results in numerous craniofacial defects. In this study we have attempted to define the point at which cephalic neural crest development is disrupted in ET(A)-deficient embryos. We find that, while neural crest cell migration in the head of ET(A)(-/-) embryos appears normal, expression of a number of transcription factors in the arch ectomesenchymal cells is either absent or significantly reduced. These ET(A)-dependent factors include the transcription factors goosecoid, Dlx-2, Dlx-3, dHAND, eHAND, and Barx1, but not MHox, Hoxa-2, CRABP1, or Ufd1. In addition, the size of the arches in E10.5 to E11.5 ET(A)(-/-) embryos is smaller and an increase in ectomesenchymal apoptosis is observed. Thus, ET(A) signaling in ectomesenchymal cells appears to coordinate specific aspects of arch development by inducing expression of transcription factors in the postmigratory ectomesenchyme. Absence of these signals results in retarded arch growth, defects in proper differentiation, and, in some mesenchymal cells, apoptosis. In particular, this developmental pathway appears distinct from the pathway that includes UFD1L, implicated as a causative gene in CATCH 22 patients, and suggests parallel complementary pathways mediating craniofacial development.
    [Abstract] [Full Text] [Related] [New Search]