Interactions of Ectodysplasin and Wnt in Hair Follicle Development

December 2007
By Sarah E. Millar, PhD, M8 Stellar-Chance Laboratories

Hypohidrotic ectodermal dysplasia is a congenital syndrome characterized by defective hair growth, missing and abnormally shaped teeth, and absence of sweat glands. There is a set of genes whose products normally interact with each other to regulate the development of hair follicles, teeth and sweat glands during gestation. When one of these genes and its encoded protein is defective, abnormal formation of these organs occurs.

A key gene in this process is Eda, which codes for a small protein that binds to a receptor known as Edar. Defects in Eda or Edar cause HED in humans and in mice, indicating that mice provide an excellent model system for investigating the molecular basis of human ectodermal dysplasias.

Exciting recent findings demonstrated that forced activation of a molecular signaling pathway, known as the Wnt / ß–catenin pathway, is capable of forming new hair follicles in adults. Regulation of cell-cell communication by Wnt proteins is necessary for early stages in the development of hair follicles, teeth and other organs affected in ED syndromes. These findings suggest manipulation of the Wnt pathway as a possible therapeutic approach for hair and tooth defects in individuals affected by ED syndromes.

The researchers are using a mouse model to test whether forced activation of Wnt / ß–catenin signaling can cause the formation of new hair follicles in a mouse model for HED, and, if so, whether the hair follicles develop normally. Their initial results confirm the ability to induce new hair follicles in adult mouse skin by introducing an activated form of ß–catenin. These engineered mice are currently being crossed to the mutant HED mice. These experiments will provide essential information for the design of novel therapies for adults affected by ED syndromes

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