The human brain is composed of 1011 neurons which make 1014 synaptic connections. How each of these neurons acquires a unique identity and is directed to its appropriate target are central questions in developmental biology. One approach for Investigating mechanisms that generate this enormous cell diversity is to ask the simple question: How can the division of a single neuronal progenitor give rise to two daughter neurons with alternative fates? This proposal addresses this question by examining the developmental pathway of the serotonin neurons in the ventral cord of Drosophila melanogaster. These neurons occur in pairs that are derived from a terminal mitotic division. Our preliminary data support a hypothesis that two different mechanisms are required for the specification of each daughter serotonin cell: one cell requires the function of a membrane associate protein, Numb, and the other requires the function of a nuclear transcription factor, Eagle.
The specific aims of this prop osal are designed to determine the function of these genes in development of the serotonin lineage by testing their genetic interaction with: a) each other, b) other genes that function in the development of the serotonin lineage and c) genes that show a differential expression between the two daughter serotonin neurons. These objectives will be accomplished using a combination of molecular genetics, immunohistochernistry and confocal microscopy. The process of specifying cell fate involves both intrinsic cytoplasmic factors and extrinsic signaling from neighboring cells. The serotonin neurons offer a unique opportunity to study the integration of these mechanisms during central nervous system development. In addition to providing a relatively simple lineage to examine cell fate specification, the serotonin neurons are also interesting from a physiological perspective. Serotonin is a conserved neurotransmitter throughout the animal kingdom and has been demonstrated to be involved in learning, memory and locomotion in both invertebrates and vertebrates. In humans altered serotonin levels have been associated with several disorders such as Alzheimer's, schizophrenia, depression, aggression and drug addiction. In the long-term an understanding of the developmental pathway for serotonin neurons in Drosophila will allow manipulation of these cells and investigation of the physiological properties that underlie serotonin neurotransmission.
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