Title: Mechanisms of sexually dimorphic development in the nervous system of Caenorhabditis elegans
Description: The advent of sexual reproduction in early evolutionary history had profound effects on the evolution of animals. In most sexually reproducing species, males and females have distinct morphological and behavioral differences that are shaped by the evolutionary imperatives of each sex. Underlying the behavioral differences between males and females are distinct and measurable dimorphisms in the nervous system. These dimorphisms can arise in the form of connectivity, neurotransmitter usage, gene expression or combinations of all three. The androdioecious nematode Caenorhabditis elegans, with its stereotyped development and simple nervous system, offers a remarkably powerful system for studying the conserved mechanisms of sex determination that shape neural development. In this thesis, I present my work on the characterization of several genes that regulate the development of sexual dimorphisms in the nervous system. The first part of the thesis concerns the characterization of the gene ham-3, which codes for a subunit of the C. elegans ortholog of the SWI/SNF chromatin remodeling complex. ham-3 is required for the proper terminal differentiation of the HSN, a serotonergic neuron of the sex-specific nervous system, which it manages by regulating the expression of transcription factors required for crucial steps of migration, axon guidance and serotonergic fate adoption.

The second part of the thesis concerns the investigation of sexually dimorphic pruning mechanisms. I show that unc-6/Netrin is subject to direct transcriptional repression in hermaphrodites by tra-1, the master transcriptional regulator of sexual fate determination in C. elegans. This regulation is required for the proper timing of the sexually dimorphic pruning of synapses in the tail region in hermaprhodites. In males, where unc-6 is not repressed by tra-1, unc-6 expression perdures into adulthood and the synapse is maintained. Together, these data provide insight into the ways in which conserved genetic and developmental mechanisms manage the generation differentiation, connectivity, and maintenance of sexually dimorphic nervous systems.