Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons

Amy Greenstein Baynash, Kiminori Hosoda, Adel Giaid, James A Richardson, Noriak Emoto, Robert E Hammer, Masashi Yanagisawa

Research output: Contribution to journalArticle

764 Citations (Scopus)

Abstract

Defects in the gene encoding the endothelin-B receptor produce aganglionic megacolon and pigmentary disorders in mice and humans. We report that a targeted disruption of the mouse endothelin-3 ligand (EDN3) gene produces a similar recessive phenotype of megacolon and coat color spotting. A natural recessive mutation that results in the same developmental defects in mice, lethal spotting (ls), failed to complement the targeted EDN3 allele. The ls mice carry a point mutation of the EDN3 gene, which replaces the Arg residue at the C-terminus of the inactive intermediate big EDN3 with a Trp residue. This mutation prevents the proteolytic activation of big EDN3 by ECE-1. These findings indicate that interaction of EDN3 with the endothelin-B receptor is essential in the development of neural crest-derived cell lineages. We postulate that defects in the human EDN3 gene may cause Hirschsprung's disease.

Original languageEnglish (US)
Pages (from-to)1277-1285
Number of pages9
JournalCell
Volume79
Issue number7
DOIs
StatePublished - Dec 30 1994

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Endothelin-3
Endothelin B Receptors
Melanocytes
Neurons
Ligands
Metrorrhagia
Hirschsprung Disease
Genes
Defects
Megacolon
Mutation
Gene encoding
Neural Crest
Cell Lineage
Point Mutation
Color
Chemical activation
Alleles
Phenotype

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. / Baynash, Amy Greenstein; Hosoda, Kiminori; Giaid, Adel; Richardson, James A; Emoto, Noriak; Hammer, Robert E; Yanagisawa, Masashi.

In: Cell, Vol. 79, No. 7, 30.12.1994, p. 1277-1285.

Research output: Contribution to journalArticle

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AU - Emoto, Noriak

AU - Hammer, Robert E

AU - Yanagisawa, Masashi

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AB - Defects in the gene encoding the endothelin-B receptor produce aganglionic megacolon and pigmentary disorders in mice and humans. We report that a targeted disruption of the mouse endothelin-3 ligand (EDN3) gene produces a similar recessive phenotype of megacolon and coat color spotting. A natural recessive mutation that results in the same developmental defects in mice, lethal spotting (ls), failed to complement the targeted EDN3 allele. The ls mice carry a point mutation of the EDN3 gene, which replaces the Arg residue at the C-terminus of the inactive intermediate big EDN3 with a Trp residue. This mutation prevents the proteolytic activation of big EDN3 by ECE-1. These findings indicate that interaction of EDN3 with the endothelin-B receptor is essential in the development of neural crest-derived cell lineages. We postulate that defects in the human EDN3 gene may cause Hirschsprung's disease.

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