May 2005

Royal Melbourne researchers find genetic key to skin formation

Researchers at the Royal Melbourne Hospital have cracked a 700 million-year-old genetic code.

They have identified the gene in mice responsible for healing wounds and forming the body’s protective barrier–—skin.

The discovery by researchers at the hospital’s Bone Marrow Research Laboratories could impact on the treatment in humans of cancer, wounds, burns and surgical incisions, said Laboratory Director and its principal Research Fellow Associate Professor Stephen Jane.

It could also improve the care of infants born prematurely and lacking a properly-formed protective skin.

Announced in the latest edition of leading international medical and scientific research journal Science, the discovery coincided with similar findings—also published in the same edition of the journal—by United States researchers studying the skin of flies.

Dr Jane said because the structure of DNA in mice and humans was almost identical, the identification of this gene in mice had direct implications for humans.

‘Human skin—like mouse skin—acts as a vital barrier for the body, protecting it from dehydration and infection.

Until now, we have been unsure of the mechanics involved in the formation of the skin as a barrier and in wound healing.

‘As we begin to understand the basic biology governing these processes we can begin to develop therapeutic approaches directly targeted at this important gene,’ said Dr Jane.

Mice deficient in this gene died at birth from dehydration as the outer barrier layer of their skin was defective, which allowed excessive water loss immediately after birth.

Furthermore, wounds in these mice were unable to heal, thereby identifying this gene as also critical for wound healing.

Dr Jane said the complementary study by the University of California in San Diego showed that the wound-healing and barrier function in the fly was also dependent on the fly-equivalent of this gene.

‘This indicates conservation of this function for more than 700 million years.

‘Despite the significant differences between the fly cuticle and the mammalian skin the mechanism required to form and maintain a barrier has been conserved.

‘The human gene will also have this function, given the relatively small evolutionary distance between mouse and man compared with fly and mouse.’

By further studying the cellular effects of this gene, researchers will not only gain new insights into wound healing but may also discover how the cell machinery knows how to stop tissue growth once a wound is healed, said Dr Jane.

This extra knowledge may have implications in cancer cells as many genes activated by cancer are also activated during the process of wound healing.

The study was supported by grants from the Bone Marrow Donor Institute.