The goal of this proposal is to study the genetic and molecular mechanisms behind the differentiation and proliferation of neural precursors. Since the cells in the developing CNS are characterized by very different mitotic potentials (i.e. NBs are stem cells and GMCs each divide once), a study of genes involved in determining the unique fates of neural precursors may lead to insights into how their cell divisions are controlled. In particular, extra-extra, a gene whose mutant phenotype is defined by the presence of ectopic neurons will be cloned and characterized. Additionally, genes required for sibling neuron fates will be identified by screening for deficiencies which dominantly modify the CNS phenotype produced by loss of zygotic numb. This work may clarify general principles of asymmetric cell division as well as determine the nature of the cell-intrinsic factors or signaling pathways required for the unique identity of individual neurons. With a general understanding of how normal cell proliferation and differentiation are controlled, we should be able to improve the rationale behind cancer treatments.
