Oncology

Zebrafish dive into human genetics

The zebrafish  (Danio rerio), which looks like a small sardine, could hold the key to the genetic secret that surrounds major diseases of the human nervous system, such as schizophrenia and autism. Pierre Drapeau is willing to bet on it, as a matter of fact. The new director of the Department of Pathology and Cell Biology at the Université de Montréal recently obtained nearly $17 million to dive with his co-workers into the depths of neurological diseases, based on this vertebrate, which has a genome strangely reminiscent of the human genome. 

The zebrafish has motor functions in its vertebral column that are very close to human motor functions, such as the reflex on being touched and the swimming reflex. This genetic kinship means that researchers can use the zebrafish to test certain mutations of human genes thought to be responsible for neurological diseases. If the mutant human gene inhibits the fish’s reflex or swimming when it is substituted for the fish’s gene, the logical conclusion is that the human mutation could cause a disease.

Between the miniscule fish and the human body lies a terra incognita that the Canada Research Chair in Neuroscience is exploring step by step. “The important thing is that the more we understand about the phenotype [behaviour] of the zebrafish, the more we appreciate the subtleties of human genes. We believe that there is a defect in synaptic transmission [between neurons] at the base of several forms of psychiatric illness. Medication compensates for these defects, but what is the nature of these defects? This is where a genetic approach with an animal model can help,” says Drapeau.

The zebrafish hit the headlines with the discovery of a gene for skin colour (the article was published in the December 16, 2005, issue of the journal Science). In 1995, German scientist Christiane Nusslein-Volhard won the Nobel Prize in medicine for revealing the genes responsible for forming the human body.  Danio rerio is at the base of her most recent work.

Currently being studied by more than 1,500 researchers around the world, the zebrafish is something of a scientific celebrity. An ideal model for developmental genetics, it is used in research on cancer, heart disease, pain resistance, anemia, tissue regeneration, muscle formation, and toxicity of medications.

The only Quebec researcher working with the zebrafish,  Drapeau is very familiar with his protégé, having raised and examined many of the fish over the past decade.  It reproduces easily in limited space, it’s abundant – the female lays from 100 to 200 eggs a week – and eggs develop into embryos in just two or three days. It also has several organs in common with man, such as a heart and spinal cord.

“It’s a comprehensive model. I want to find a way to use it fully and enrich the field with its applications,” says Drapeau, whose central scientific interest is how the human brain develops into an infinite web of some 100 billion nerve cells, each of which creates thousands of synaptic contacts. He is interested in learning how neuron networks develop, form interconnections, and give birth to behaviours. A biochemist and neurophysiologist by training, he will install his 2,000 aquariums on the seventh floor of the Roger-Gaudry Pavilion this fall.  After 20 years at McGill University and with nearly 70 articles in his portfolio, Drapeau, who describes himself as having arrived at the midpoint of his life, looks forward to “the second half of my career” with great enthusiasm. “There’s an extremely refreshing vision at the Université de Montréal. People here are very directed, very well organized. That was a major factor in my decision to come here.”