The Australian zebra finch is an advantageous model for investigatingmechanisms regulating neural structure and behavior. Males and females exhibit remarkable differences in brain morphology and in the song behavior that they subserve. Thus, we can exploit these sexually dimorphic traits to begin to understand the factors that underlie development of the nervous system. While early studies implicated a critical role of estradiol (E2) in masculinizing both structure and function, Z-linked genes (males: ZZ; females: ZW) might also contribute. In the experiments conducted for this dissertation, I investigated the role of one Z-gene, tubulin specific chaperone protein A (TBCA) and its potential interactions with E2, in masculinizing the zebra finch song system. TBCA is one of several chaperone proteins involved in the formation of β-tubulin, and is critical for microtubule biosynthesis and integrity.I show that TBCA exhibits male-biased expression in the lateral magnocellularnucleus of the anterior nidopallium (LMAN). I also find that TBCA transcript and its protein product are developmentally regulated, such that this expression is higher in juveniles compared to adults. Further, TBCA is expressed in neurons that project to an efferent target, the robust nucleus of the arcopallium (RA). While the morphology of LMAN is not particularly different between the sexes, the projection from LMAN to RA is more robust in males, and this might influence masculine development of RA. Thus, TBCA is both temporally and spatially primed to influence sex-specific development.TBCA expression does not appear to be modulated by E2, as administration ofthis hormone did not influence TBCA mRNA quantity or stereological cell counts of TBCA+ cells in LMAN. However, treatment of males with the aromatase inhibitor, fadrozole, induced a hypermasculine phenotype in neural structures, including in the volume of LMAN, cell size in RA, and of the projection between these two regions.Finally, TBCA knockdown in LMAN in vivo demasculinized these samemorphological parameters in both males and females. Moreover, I did not detect an interaction between TBCA and E2 in facilitating masculine development, nor did I observe an additive effect of the two factors. Collectively, the present body of work represents an initial effort in determining the role of a Z-gene in the development of brain and behavior. The results here serve as an important platform from which wecan begin to explore the mechanisms regulating the observed effects, including those underlying cell survival and maintenance of neural projections.
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