Cell-autonomous and nonautonomous actions of endothelin-A receptor signaling in craniofacial and cardiovascular development

David E. Clouthier, S. Clay Williams, Robert E Hammer, James A Richardson, Masashi Yanagisawa

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Craniofacial and cardiac development relies on the proper patterning of the neural crest-derived ectomesenchyme of the pharyngeal arches, from which many craniofacial and great vessel structures arise. One of the intercellular signaling molecules that is involved in this process, endothelin-1 (ET-1), is expressed in the arch epithelium and influences arch development by binding to its cognate receptor, the endothelin A (ETA) receptor, found on ectomesenchymal cells. We have previously shown that absence of ETA signaling in ETA-/- mouse embryos disrupts neural crest cell development, resulting in craniofacial and cardiovascular defects similar in many aspects to those in mouse models of DiGeorge syndrome. These changes may reflect a cell-autonomous requirement for ETA signaling during crest cell development because the ETA receptor is an intracellular signaling molecule. However, it is also possible that some of the observed defects in ETA-/- embryos could arise from the absence of downstream signaling that act in a non-cell-autonomous manner. To address this question, we performed chimera analysis using ETA-/- embryonic stem cells. We observe that, in almost all early ETA -/-+/+ chimeric embryos, ETA -/- cells are excluded from the caudoventral aspects of the pharyngeal arches, suggesting a cell-autonomous role for ETA signaling in crest cell migration and/or colonization. Interestingly, in the few embryos in which mutant cells do reach the ventral arch, structures derived from this area are either composed solely of wild type cells or are missing, suggesting a second cell-autonomous role for ETA signaling in postmigratory crest cell differentiation. In the cardiac outflow tract and great vessels, ETA-/- cells are excluded from the walls of the developing pharyngeal arch arteries, indicating that ETA signaling also acts cell-autonomously during cardiac neural crest cell development.

Original languageEnglish (US)
Pages (from-to)506-519
Number of pages14
JournalDevelopmental Biology
Issue number2
StatePublished - Sep 15 2003


  • Cardiovascular
  • Chimera
  • Craniofacial
  • Mouse
  • Neural crest cell
  • Pharyngeal arch

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


Dive into the research topics of 'Cell-autonomous and nonautonomous actions of endothelin-A receptor signaling in craniofacial and cardiovascular development'. Together they form a unique fingerprint.

Cite this