The ectodysplasin pathway: from diseases to adaptations

Trends Genet. 2014 Jan;30(1):24-31. doi: 10.1016/j.tig.2013.08.006. Epub 2013 Sep 23.

Abstract

The ectodysplasin (EDA) pathway, which is active during the development of ectodermal organs, including teeth, hairs, feathers, and mammary glands, and which is crucial for fine-tuning the developmental network controlling the number, size, and density of these structures, was discovered by studying human patients affected by anhidrotic/hypohidrotic ectodermal dysplasia. It comprises three main gene products: EDA, a ligand that belongs to the tumor necrosis factor (TNF)-α family, EDAR, a receptor related to the TNFα receptors, and EDARADD, a specific adaptor. This core pathway relies on downstream NF-κB pathway activation to regulate target genes. The pathway has recently been found to be associated with specific adaptations in natural populations: the magnitude of armor plates in sticklebacks and the hair structure in Asian human populations. Thus, despite its role in human disease, the EDA pathway is a 'hopeful pathway' that could allow adaptive changes in ectodermal appendages which, as specialized interfaces with the environment, are considered hot-spots of morphological evolution.

Keywords: adaptation; anhidrotic/hypohidrotic ectodermal dysplasia; ectodermal appendages; ectodysplasin; signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological / genetics*
  • Animals
  • Ectodermal Dysplasia 1, Anhidrotic / genetics*
  • Ectodysplasins / genetics*
  • Ectodysplasins / metabolism
  • Edar Receptor / genetics
  • Edar Receptor / metabolism
  • Edar-Associated Death Domain Protein / genetics
  • Edar-Associated Death Domain Protein / metabolism
  • Gene Expression Regulation
  • Humans
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism
  • Signal Transduction
  • Vertebrates / genetics

Substances

  • Ectodysplasins
  • Edar Receptor
  • Edar-Associated Death Domain Protein
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor