EDN3endothelin3

EDN3, also known as endothelin-3, is a member of the endothelin family of potent vasoactive peptides. The EDN3 gene encodes preproendothelin-3, which is processed by endothelin-converting enzymes to form the active peptide endothelin-3 (ET-3). ET-3 signals mainly through endothelin receptors, with a preference for the endothelin receptor type B (EDNRB); it has comparatively low activity at endothelin receptor type A (EDNRA).

ET-3 is expressed in neural crest–derived tissues and plays a crucial role in development, particularly in the enteric nervous system and melanocyte lineage. The ET-3/EDNRB signaling axis influences the migration, proliferation, and survival of enteric neural crest cells, and it contributes to pigment cell development. Proper ET-3 signaling is essential for the formation of enteric ganglia and normal pigmentation.

Clinical significance of EDN3 includes its involvement in neurocristopathies. Mutations or disrupted signaling in EDN3 or its receptor EDNRB are associated with Hirschsprung disease, which is characterized by aganglionosis of the distal bowel and intestinal obstruction. Waardenburg syndrome type 4, which combines pigmentary abnormalities with Hirschsprung disease, can arise from mutations in EDN3 or EDNRB. While most EDN3-related effects are congenital, ongoing research continues to explore their roles in vascular biology and pigmentary disorders.

References to EDN3 frequently appear alongside discussions of the endothelin signaling pathway, EDNRB, and EDNRA, reflecting their interconnected roles in neural crest development and related phenotypes.