Mammals also contain at least two close relatives of p53, but at present we know far less about the roles they play. We do know that one of the relatives, p63, is absolutely necessary for generation of skin in vertebrate embryos.

Mice with mutations in p63 die shortly after birth and exhibit severe developmental defects, including lack of skin, hair, whiskers, teeth and limbs.

Two studies published in the May issue of Developmental Cell provide an in-depth examination of the precise role of p63 in skin development. Because detailed studies examining the function and regulation of the different forms of p63 are difficult to conduct and interpret in developing embryos of higher vertebrates, both research groups made use of zebrafish embryos as a model system.

Very early in development, embryonic cells called ectoderm are fated to develop into skin (epidermal) cells or neural cells, depending on the signals they receive. It is known that ectodermal cells will automatically develop into neural cells unless they receive an appropriate inhibitory signal.

Dr. Matthias Hammerschmidt from the Max-Planck Institute in Freiburg, Germany, and colleagues, designed a series of studies to examine whether p63 was involved in this early step of skin cell differentiation. They found that p63 acted as a repressor for development of neural tissue and stimulated production of epidermal cells. The researchers demonstrated that 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 from the University of Washington in Seattle, WA, examined the role of p63 slightly later in development. Proliferation of skin cells was essentially eliminated when a specific form of p63 was mutated. However, other parts of the embryo continued to grow normally for the first few days of development. They reported this particular form of p63 functioned to inhibit p53 and thus stimulated the rapid proliferation of epidermal cells needed for skin growth and limb development.

Results from both of these studies suggest a model in which the role of p63 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.

In addition to adding to our knowledge of what drives development of the skin, the reported inhibition of p53 by p63 and resulting stimulation of cell proliferation has interesting implications for cancer research.

(Reference: Developmental Cell Volume 2 Number 5 May 2002.)


[Contact: Dr. Matthias Hammerschmidt, Dr. David Kimelman]

10-May-2002