Dual genetic pathways of endothelin-mediated intercellular signaling revealed by targeted disruption of endothelin converting enzyme-1 gene - PubMed (original) (raw)

. 1998 Mar;125(5):825-36.

doi: 10.1242/dev.125.5.825.

Affiliations

• PMID: 9449665
• DOI: 10.1242/dev.125.5.825

Dual genetic pathways of endothelin-mediated intercellular signaling revealed by targeted disruption of endothelin converting enzyme-1 gene

H Yanagisawa et al. Development. 1998 Mar.

Abstract

Recent gene targeting studies have revealed unexpected roles for endothelins in the development of neural crest-derived tissues. Endothelin converting enzyme-1 (ECE-1) catalyzes the proteolytic activation of big endothelin-1 to endothelin-1(ET-1) in vitro. However, the importance of ECE-1 cleavage in the multiple endothelin pathways in vivo is unknown. Here we generated a targeted null mutation in the mouse ECE-1 gene. ECE-1-/- term embryos exhibited craniofacial and cardiac abnormalities virtually identical to the defects seen in ET-1 and endothelin A receptor (ETA)-deficient embryos. Epidermal melanocytes as well as enteric neurons of the distal gut were also absent in ECE-1-/- embryos, reproducing the developmental phenotype seen in ET-3-/- and endothelin B receptor (ETB)-/- mice. Surprisingly, large amounts of mature ET-1 peptide are found in ECE-1-/- embryos, indicating that non-ECE-1 protease(s) can activate ET-1 at certain sites. However, these enzymes cannot produce sufficient mature endothelin at the locations crucial for normal embryonic development. These findings reveal that ECE-1 is a bona fide activating protease for both big ET-1 and big ET-3 in vivo, and that the cell-cell communication pathways represented by the ET-1/ECE-1/ETA axis and the ET-3/ECE-1/ETB axis are each involved in the development of distinct subsets of neural crest cell lineages. Mutations in ECE-1 may cause developmental defects in humans, such as Hirschsprung disease, velocardiofacial syndrome and related neurocristopathies.

PubMed Disclaimer

Similar articles

• Disruption of ECE-1 and ECE-2 reveals a role for endothelin-converting enzyme-2 in murine cardiac development.
  Yanagisawa H, Hammer RE, Richardson JA, Emoto N, Williams SC, Takeda Si, Clouthier DE, Yanagisawa M. Yanagisawa H, et al. J Clin Invest. 2000 May;105(10):1373-82. doi: 10.1172/JCI7447. J Clin Invest. 2000. PMID: 10811845 Free PMC article.
• Role of Endothelin-1/Endothelin-A receptor-mediated signaling pathway in the aortic arch patterning in mice.
  Yanagisawa H, Hammer RE, Richardson JA, Williams SC, Clouthier DE, Yanagisawa M. Yanagisawa H, et al. J Clin Invest. 1998 Jul 1;102(1):22-33. doi: 10.1172/JCI2698. J Clin Invest. 1998. PMID: 9649553 Free PMC article.
• Endothelin-converting enzyme-2 is a membrane-bound, phosphoramidon-sensitive metalloprotease with acidic pH optimum.
  Emoto N, Yanagisawa M. Emoto N, et al. J Biol Chem. 1995 Jun 23;270(25):15262-8. doi: 10.1074/jbc.270.25.15262. J Biol Chem. 1995. PMID: 7797512
• Molecular pharmacology of endothelin converting enzymes.
  Turner AJ, Murphy LJ. Turner AJ, et al. Biochem Pharmacol. 1996 Jan 26;51(2):91-102. doi: 10.1016/0006-2952(95)02036-5. Biochem Pharmacol. 1996. PMID: 8615890 Review.
• Endothelin.
  Davenport AP, Maguire JJ. Davenport AP, et al. Handb Exp Pharmacol. 2006;(176 Pt 1):295-329. doi: 10.1007/3-540-32967-6_9. Handb Exp Pharmacol. 2006. PMID: 16999223 Review.

Cited by

• Competition between Jagged-Notch and Endothelin1 Signaling Selectively Restricts Cartilage Formation in the Zebrafish Upper Face.
  Barske L, Askary A, Zuniga E, Balczerski B, Bump P, Nichols JT, Crump JG. Barske L, et al. PLoS Genet. 2016 Apr 8;12(4):e1005967. doi: 10.1371/journal.pgen.1005967. eCollection 2016 Apr. PLoS Genet. 2016. PMID: 27058748 Free PMC article.
• Endothelin signaling in development.
  Kanai SM, Clouthier DE. Kanai SM, et al. Development. 2023 Dec 15;150(24):dev201786. doi: 10.1242/dev.201786. Epub 2023 Dec 11. Development. 2023. PMID: 38078652 Free PMC article. Review.
• Building a brain in the gut: development of the enteric nervous system.
  Goldstein AM, Hofstra RM, Burns AJ. Goldstein AM, et al. Clin Genet. 2013 Apr;83(4):307-16. doi: 10.1111/cge.12054. Epub 2012 Nov 27. Clin Genet. 2013. PMID: 23167617 Free PMC article. Review.
• Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer.
  Charité J, McFadden DG, Merlo G, Levi G, Clouthier DE, Yanagisawa M, Richardson JA, Olson EN. Charité J, et al. Genes Dev. 2001 Nov 15;15(22):3039-49. doi: 10.1101/gad.931701. Genes Dev. 2001. PMID: 11711438 Free PMC article.
• Reduced fertility in male mice deficient in the zinc metallopeptidase NL1.
  Carpentier M, Guillemette C, Bailey JL, Boileau G, Jeannotte L, DesGroseillers L, Charron J. Carpentier M, et al. Mol Cell Biol. 2004 May;24(10):4428-37. doi: 10.1128/MCB.24.10.4428-4437.2004. Mol Cell Biol. 2004. PMID: 15121861 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Silverchair Information Systems

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)

• Research Materials

  • Jackson Laboratory JAX®Mice Database