Scientists at The Hospital for Sick Children (SickKids) have linked known cancer-causing genes to normal developmental processes as well as wound healing using a fruit fly model. This research in reported in the cover article of the July 24 issue of the scientific journal Current Biology.

The laboratory of SickKids developmental biologist Howard Lipshitz studies a process called morphogenesis — the construction of tissues and organs from simple sheets of cells. Understanding morphogenesis is key to discovering what happens when development goes wrong, as is the case in congenital birth defects or diseases such as cancer.

Dr. Bruce Reed, a postdoctoral fellow in Dr. Lipshitz’s lab, studied how two sheets of cells move over an underlying layer of cells and then zipper up to form a seam. This process is necessary to seal the epidermis (skin) of the embryo around the internal tissues and organs.

“This zippering up is not only crucial for construction of the organism, it is also a model for how the body repairs wounds in humans,” explained Dr. Reed, the study’s lead author.

The process of zippering up is controlled by signals that activate two master regulatory proteins called Jun and Fos. Jun and Fos are referred to as oncogenes because, when mutated in mammals, they can cause cancer.

“By using the fruit fly as a model, we can investigate what these genes do in a normal and a mutant state. Jun and Fos receive signals as to when they should turn off and on, in order to control normal developmental processes such as the zippering up of the epidermis. We are excited about investigating what happens to the healing process when the cancer-causing versions of the Jun and Fos proteins are turned on during development,” said Dr. Lipshitz, head and senior scientist of Developmental Biology in the HSC Research Institute and a professor of Medical Genetics and Microbiology at the University of Toronto.

There are significant genetic similarities between human beings and Drosophila (fruit flies) in that they share many of the genes that are crucial for development and survival. Two out of three human disease genes have been shown to have counterparts in Drosophila. This makes the fruit fly a premier model for studying the molecular basis of human diseases.

“Fruit flies provide an invaluable model for studying complex processes that also occur in the human body. The have a short life span, which allows us to study genetic changes over multiple generations in a short time,” Dr. Reed added.

Fruit flies were first used in biomedical research in the early 1900s. The high points of a century of work on fruit flies include proof that genes are located on chromosomes; that large doses of x-rays and other forms of ionizing radiation cause genetic mutations; and that the master regulatory genes controlling animal development have been conserved in evolution.

This research was supported by the National Cancer Institute of Canada with funds from the Canadian Cancer Society.