EDN3geenien

EDN3genen refers to the genes encoding endothelin-3, a peptide that is part of the endothelin signaling system in vertebrates. The endothelin family includes three peptides—endothelin-1, endothelin-2, and endothelin-3—each produced from separate genes. The EDN3 gene encodes a prepropeptide that is processed by proteases such as furin-like convertases and endothelin-converting enzymes to yield the active endothelin-3 peptide.

Biological role and expression: Endothelin-3 is expressed in neural crest–derived tissues during development and mainly signals through the endothelin receptor type B (EDNRB). Through EDNRB, EDN3 regulates the migration, proliferation, and survival of neural crest cells that form the enteric nervous system and pigment cells of the skin and hair. Proper EDN3/EDNRB signaling is thus important for the development of the enteric nervous system and for melanocyte lineage formation in many species.

Receptors and signaling: Endothelin-3 has high affinity for EDNRB, which mediates many of its developmental effects. EDNRB signaling can influence gut innervation, pigment cell development, and related processes. The closely related receptor EDNRA binds endothelin peptides with different affinities, and receptor usage can influence tissue-specific responses.

Clinical significance: Mutations or disruptions in EDN3 or in the EDNRB signaling axis can contribute to congenital disorders such as Hirschsprung disease, in which the enteric nervous system is absent from parts of the intestine. Mutations in EDN3 or EDNRB have also been associated with Waardenburg syndrome type IV, which features pigmentary abnormalities and sometimes deafness. Animal models, including mice, show that loss of Edn3 or EdnrB impairs enteric nervous system development and melanocyte formation.

Genomic context and evolution: The EDN3 gene is part of a conserved endothelin gene family present across vertebrates, reflecting an ancient duplication and diversification that yields distinct peptides with overlapping yet specialized roles in neural crest development and vascular biology.