The proposed studies will elucidate the roles of five genes and their protein products in the development of brain and behavior. They focus on sexual differentiation of the structure and function of the song control system in the forebrain of zebra finches. Only males sing, and the brain areas that control song are far larger in males, which is due to males having more and larger cells in these regions than females. In many vertebrates, the development of these types of male-biased differences in behavior and morphology is regulated mainly by gonadal steroids. However, in some mammalian systems, sexual differentiation is controlled more directly by the expression of genes. In zebra finches, the evidence suggests that both are involved. The present proposal will test the hypothesis that masculinization of the zebra finch song system is controlled by genes, including those on the Z-chromosome (unlike XX/XY mammals, male zebra finches are ZZ and females are ZW), that influence the response of the brain to steroid hormones. The work involves characterization of five genes we recently identified in the zebra finch brain with enhanced expression in song control nuclei in males compared to females. These genes include those encoding ribosomal proteins L17 and L37, secretory carrier membrane protein 1 (SCAMP1), zinc finger protein 216 (ZNF216) and a COBW-domain containing protein. We will complete the sequence analysis for these genes, confirm their locations on zebra finch chromosomes, and determine the time-course of their sexually dimorphic expression within the song circuit and related regions. The effects of inhibiting their function on development of song learning and masculinization of song system morphology will be elucidated. In addition, interactions between the genes and steroid hormone will be investigated. For example, the role of estradiol in the expression of the genes and potential interactions with androgen receptors, both of which are involved in masculinization, will be studied. Very little information is available in the literature on these genes, so as this work is pursued, we will learn not only more about mechanisms regulating sexual differentiation, but also about the genes themselves. Most importantly, however, the proposed studies will elucidate mechanisms critical for normal development of brain structure and function, and can lead to the discovery of solutions to problems, including those associated with disease, injury, aging and contaminant exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH055488-15
Application #
7813991
Study Section
Special Emphasis Panel (ZRG1-IFCN-H (02))
Program Officer
Panchision, David M
Project Start
1996-06-01
Project End
2011-06-30
Budget Start
2010-06-01
Budget End
2011-06-30
Support Year
15
Fiscal Year
2010
Total Cost
$307,140
Indirect Cost
Name
Michigan State University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Qi, L M; Wade, J (2013) Sexually dimorphic and developmentally regulated expression of tubulin-specific chaperone protein A in the LMAN of zebra finches. Neuroscience 247:182-90
Ball, Gregory F; Wade, Juli (2013) The value of comparative approaches to our understanding of puberty as illustrated by investigations in birds and reptiles. Horm Behav 64:211-4
Wade, Juli; Peabody, Camilla; Tang, Yu Ping et al. (2013) Estradiol modulates neurotransmitter concentrations in the developing zebra finch song system. Brain Res 1517:87-92
Wade, Juli; Lampen, Jennifer; Qi, Linda et al. (2013) Norepinephrine inhibition in juvenile male zebra finches modulates adult song quality. Brain Res Bull 90:132-6
Tang, Yu Ping; Wade, Juli (2012) 17?-estradiol regulates the sexually dimorphic expression of BDNF and TrkB proteins in the song system of juvenile zebra finches. PLoS One 7:e43687
Qi, Linda M; Mohr, Margaret; Wade, Juli (2012) Enhanced expression of tubulin-specific chaperone protein A, mitochondrial ribosomal protein S27, and the DNA excision repair protein XPACCH in the song system of juvenile male zebra finches. Dev Neurobiol 72:199-207
Tang, Y P; Wade, J (2011) Developmental changes in the sexually dimorphic expression of secretory carrier membrane protein 1 and its co-localisation with androgen receptor protein in the zebra finch song system. J Neuroendocrinol 23:584-90
Thompson, J Bayley; Dzubur, Eldin; Wade, Juli et al. (2011) The effects of estradiol on 17?-hydroxysteroid dehydrogenase type IV and androgen receptor expression in the developing zebra finch song system. Brain Res 1401:66-73
Tang, Y P; Wade, J (2010) Sex- and age-related differences in ribosomal proteins L17 and L37, as well as androgen receptor protein, in the song control system of zebra finches. Neuroscience 171:1131-40
Wu, Di; Tang, Yu Ping; Wade, Juli (2010) Co-localization of sorting nexin 2 and androgen receptor in the song system of juvenile zebra finches. Brain Res 1343:104-11

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