The Dual Role of p63 Gene in Skin Development

Researchers using zebrafish embryos as a model system have defined the two-fold mode of action of the p63 gene, which plays a critical role in the formation of skin in the developing embryo. Their findings were published in two articles in the May 2002 issue of Developmental Cell. Mice with mutations in p63 die shortly after birth and exhibit severe developmental defects, including lack of skin, hair, whiskers, teeth and limbs.

Dr. Matthias Hammerschmidt from the Max-Planck Institute (Freiburg, Germany) and colleagues designed a series of studies to examine at what stage p63 becomes involved in the process of skin cell differentiation. They found that p63 acted as a repressor of the development of neural tissue but stimulated production of epidermal cells. Loss of p63 resulted in an increase in neural tissue and loss of skin and fin bud formation. In contrast, when p63 was artificially turned on, neural development was blocked.

Dr. David Kimelman and associates from the University of Washington (Seattle WA, USA) examined the role of p63 slightly later in development. They found that when a specific form of p63 was mutated, proliferation of skin cells was essentially eliminated. Other parts of the embryo continued to grow normally for the first few days of development. This particular form of p63 functioned to inhibit the cancer suppressing p53 gene and thus stimulated the rapid proliferation of epidermal cells needed for skin growth and limb development.

The effect of p63 on skin formation is two-fold. Initially, p63 functions to suppress development of neural tissue, allowing ectodermal cells to differentiate into early skin cells. Later, p63 functions to stimulate rapid proliferation of the skin cells.



Related Links:
University of Washington
Max-Planck Institute