EDN3EDNRB

EDN3EDNRB refers to the signaling interaction between endothelin-3 (EDN3) and its receptor endothelin receptor type B (EDNRB). In vertebrates, EDN3 is a peptide ligand that binds specifically to EDNRB, a G protein-coupled receptor expressed on various neural crest–derived cell lineages. The EDN3-EDNRB axis is a key component of endothelin signaling, influencing intracellular calcium levels and downstream pathways that regulate cell proliferation, migration, survival, and differentiation.

During development, the EDN3-EDNRB pathway plays a critical role in neural crest–derived tissues, including the enteric nervous system, melanocytes, and certain peripheral ganglia. Proper signaling promotes the colonization of the gut with enteric neurons and the development of pigment cells; disruptions of this axis can impair neural crest cell migration and maturation.

Genetic mutations affecting either EDN3 or EDNRB are associated with diseases such as Hirschsprung disease, characterized by congenital aganglionosis of the distal intestine, and can contribute to pigmentary abnormalities. In some cases, mutations or interacting genetic factors involving EDNRB contribute to Waardenburg syndrome type 4, which combines Hirschsprung disease with pigmentary defects and deafness. The EDN3-EDNRB axis also intersects with broader developmental pathways and has been studied in contexts such as melanoma and other neural crest–derived tissues.

Therapeutically, endothelin signaling is a target in several conditions, though therapies specifically modulating the EDN3-EDNRB interaction are primarily at the research stage. The axis remains a focus for understanding neural crest biology and related congenital disorders.