Ectodysplasin signaling in development

Abstract

Ectodysplasin (Eda), a signaling molecule belonging to the tumor necrosis factor family, is required for normal development of several ectodermally derived organs in humans and mice. Two closely related isoforms of ectodysplasin, Eda-A1 and Eda-A2, have been described which bind to and activate two different receptors, Edar and X-linked Eda-A2 receptor (Xedar), respectively. Mutations in Eda, Edar or other molecules of this signaling pathway cause ectodermal dysplasias characterized by defective development of teeth, hairs, and several exocrine glands such as sweat glands presumably due to impaired NF-kappaB response. Studies with mice either lacking the functional proteins of Edar pathway or overexpressing the ligand or receptor suggest that Eda-A1-Edar signaling has multiple roles in ectodermal organ development regulating their initiation, morphogenesis, and differentiation.