The diversity of cell types in the nervous system has been recognized for over a century, yet our understanding of the developmental processes that give rise to such a complex and functionally diverse organ is far from complete. The investigation of both vertebrate and invertebrate nervous systems has elucidated many of the basic mechanisms of early neuronal specification and has shown them to be largely conserved. However, the terminal stages of neuron class and subclass specification have only been studied in a few examples. In this thesis, I investigate the terminal mechanisms of neuron fate specification through the analysis of a pair of gustatory neurons, the ASE neurons, in the nematode Caenorhabditis elegans. The ASE neuron class can be subdivided into two subclasses; a functionally distinct ASE left (ASEL) neuron and an ASE right (ASER) neuron.
In an effort to better understand the molecular composition and developmental mechanisms that program the ASE gustatory neuron class, a SAGE library for the ASE neurons was generated in collaboration with Don Moerman's group at the University of British Columbia and identified more than 1000 genes that specifically define the ASE gustatory neuron class on a molecular level. I next characterized the role of the Zn finger transcription factor, che-1, in ASE class and subclass specification. I identified a common cis-regulatory motif (the “ASE motif”) in the cis-regulatory sequences of many ASE-expressed gene and showed it to be a binding site for CHE-1. I have additionally shown that both neuron class specification and subclass specification depend on the CHE-1 binding site. In the case of left/right diversification, the activity of the ASE motif is controlled through a diverse set of additional cis-regulatory elements in the promoter of asymmetrically expressed terminal differentiation genes.
This thesis provides insights into the terminal mechanisms of neuronal fate specification, demonstrating that the activity of a neuron type specific selector gene is modulated by a variety of distinct means to diversify individual neuron classes into specific subclasses. These results expand our understanding of the regulatory logic of neuronal specification in C. elegans and across metazoans in general.
|School Location:||United States -- New York|
|Source:||DAI-B 69/10, Dissertation Abstracts International|
|Keywords:||Gustatory neurons, Nervous system, Neuron development, cis-regulatory logic|
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