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Mission

Our genetic screens have identified several mutant lines that disrupt normal neural development in the mouse. We combine genetic, biochemical and cell biological approaches to identify the pathways in which the affected proteins act and identify the molecular mechanism through which they function. Unexpectedly, things we never suspected to be important in the formation of the nervous system are revealing themselves as being essential. For example, one of our mutant lines results abnormal neural cell specification due to a structural defect in cilia. Furthermore, the affected protein does not have a invertebrate homologue highlighting the need to study mammalian development in mammals. Through our studies, we aim to understand the gene networks that direct normal neural development.

Background

The amazing advances that have been made in understanding how the human nervous system is formed (development) and is diseased (cancer) have for the most part been driven by “educated guesses”. The same genes that form the nervous system in flies and worms are often important in the development of the human brain. But flies and worms are not mammals, and “educated guesses” are inherently biased. Therefore, our lab uses an unbiased approach where we allow biology to teach us what it needs to form the mammalian nervous system. We generate random mutations in the DNA of mice and then ask which mutations affect the development of the brain. In this manner, things we may not have suspected to be important in the formation of the nervous system are revealing themselves as being essential.