Date of Award

11-21-2008

Degree Type

Closed Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

First Advisor

Laura Carruth - Chair

Second Advisor

Gregory F. Ball

Third Advisor

Matthew S. Grober

Fourth Advisor

Larry J. Young

Fifth Advisor

Elliott Albers

Abstract

The Australian zebra finch (Taeniopygia guttata) serves as an excellent model organism for studying the mechanisms that influence brain sexual differentiation. The brain and behavior of the zebra finch are sexually dimorphic. The regions of the brain that control the learning and production of song (song control nuclei) are significantly larger in the male brain than in the female brain and only males sing courtship songs, thus the majority of past research has focused on the development of these sex differences. In the majority of mammals, brain sexual differentiation occurs because hormones secreted from the gonads act to initiate male or female brain development. In zebra finches, estradiol is sufficient to masculinize the male brain, however manipulations of developmental hormone exposure fail to fully reverse the sex differences in song nuclei size. Furthermore, genetic females induced to develop functional testicular tissue do not develop a completely masculinized song system and castration has no effect on development of the song system in males. The source of the increased estrogenic signal in male zebra finch brain has yet to be identified, but data suggest that other neuronal factors play a role in development of the song control nuclei. Coregulators, such as coactivators and corepressors, are proteins and RNA activators that work by enhancing or depressing transcriptional activity of the nuclear steroid receptor with which they associate. Coregulators also modulate the development of sex-specific brain morphology and behavior in rodents and birds and may help to explain the difficulties observed in altering song nuclei development via castration and gonadal hormone replacement. As an estrogen receptor-α coactivator, ribosomal protein L7 (RPL7) is able to make the brain more sensitive to estradiol by enhancing the effects of steroid receptor action. Therefore, this dissertation addressed the following questions regarding RPL7: (1) is RPL7 expression sexually dimorphic in the song nuclei of the zebra finch brain?; (2) is RPL7 protein expression regulated by steroid hormones?; and (3) does decreasing RPL7 protein expression with antisense oligonucleotides alter neuronal survival in vivo and song nuclei size and neuron number in vitro? Collectively, these studies will provide valuable information about the role of steroid receptor coactivators in development of the zebra finch song system and on the role of coactivators on sexual differentiation of the brain.

Share

COinS