The mammalian central nervous system (CNS) contains a most diverse group of neurons. How are neuronal cell fate specified during development? Relatively little is known about the molecular mechanisms utilized in generating cell diversity in the vertebrate CNS. Our approach to this problem is to make use of the wealth of information gathered from the study of neuronal cell fate specification in the fruit fly Drosophila by identifying mammalian homologs of genes which are important in fly neural development. By using our Drosophila development work as a guide, we believe that we have identified genes which are likely to play key roles in three important but relatively unexplored area of vertebrate neural development, namely neuronal cell fate specification, asymmetric cell division and initiation of axon outgrowth. Our major focus in the next few years will be the experimental tests of the following hypothesis; (1) vertebrate atonal controls the initiation of the retinal neuronal development, (2) mouse numb controls asymmetric cell division and cell lineage in mouse neurogenesis,, (3) mouse rac/cdc42 controls the neuronal morphogenesis, especially axon outgrowth and dendritic spine formation, (4) some of those genes are also involved in long term synaptic plasticity.
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