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Endothelin and neural crest development.

H Kurihara1, Y Kurihara, R Nagai

  • 1Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Japan. kuri-tky@umin.ac.jp

Cellular and Molecular Biology (Noisy-Le-Grand, France)
|October 8, 1999
PubMed
Summary
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Endothelin signaling pathways are crucial for mammalian neural crest development. Distinct ET pathways regulate cranial and trunk neural crest cells, impacting development and linked to human diseases like Hirschsprung disease.

Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Endothelins (ETs) are peptides with vasoconstrictive and proliferative activities.
  • Gene targeting research has uncovered novel roles for ETs in neural crest development.

Purpose of the Study:

  • To elucidate the distinct roles of endothelin signaling pathways in mammalian neural crest development.
  • To investigate the molecular mechanisms underlying ET-mediated neural crest development.

Main Methods:

  • Gene targeting in mice to study ET-1/ET-A and ET-3/ET-B receptor signaling.
  • Phenotypic analysis of neural crest-derived structures in knockout mice.
  • Comparison with avian neural crest ablation models.
  • Analysis of human genetic data for mutations in ET-3 and ET-B receptor genes.

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Main Results:

  • ET-1/ET-A signaling is essential for cranial/cardiac neural crest development, affecting branchial arches and great vessels.
  • ET-3/ET-B signaling is critical for trunk/vagal neural crest development, impacting enteric neurons and melanocytes, leading to megacolon and coat spotting.
  • Mutations in human ET-3 and ET-B receptor genes are associated with Hirschsprung disease.
  • Transcriptional factors HANDs and Goosecoid are implicated as downstream mediators in cranial/cardiac neural crest development.

Conclusions:

  • Distinct endothelin signaling pathways (ET-1/ET-A and ET-3/ET-B) play crucial, lineage-specific roles in mammalian neural crest development.
  • The ET system is vital for the formation of various neural crest-derived structures and is implicated in human congenital disorders.
  • Understanding these pathways provides insights into embryogenesis and related diseases.