The specific aims of our current research reflect our continued interest in understanding how the doublesex branch of the Drosophila sex determination hierarchy functions to direct growth, morphogenesis, and differentiation to build into individuals the potential for adult sexual functions. We also want to understand how information from the sex determination hierarchy is integrated with information from pattering hierarchies, in particular the HOX genes, to govern development and differentiation. We are addressing the following topics: I. How is genital imaginal disc development controlled? Our immediate goals are to: (A) understand how the functioning of the major regulatory hierarchies patterning the third instar genital disc is integrated; (B) characterize additional genes we have identified that are expressed sex-specifically or segment-specifically in the genital disc, with a strong emphasis on events likely to be immediately downstream of dsx; (C) identify direct DSX targets. II. Both the doublesex and fruitless branches of the sex hierarchy are active in gustatory sense organs on the male foreleg. We will elucidate how the two branches of the sex hierarchy act together to generate sex-specific aspects of the gustatory sensory system. III. We will test whether the female-specific doublesex protein specifies the circuitry for female sexual behavior in the nervous system. If it does, as seems likely from extant data, then we will dissect (A) how the potential for innate female sexual behaviors is built into the nervous system during development and (B) how the circuitry underlying those behaviors functions in an adult. The genes at the bottoms of the D. melanogaster sex hierarchy (doublesex and probably intersex) are evolutionarily conserved through insects to vertebrates, including human, and doublesex also functions in sexual development in mice and humans. Thus studies such as ours will provide models for understanding aspects of the fundamental biological process of sexual development. Elucidating how innate behaviors are built into nervous systems during development may provide groundbreaking insights into vast areas of nervous system development and function. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM037731-22
Application #
7265603
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Haynes, Susan R
Project Start
1978-07-01
Project End
2011-02-28
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
22
Fiscal Year
2007
Total Cost
$469,286
Indirect Cost
Name
Stanford University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Robinett, Carmen C; Vaughan, Alexander G; Knapp, Jon-Michael et al. (2010) Sex and the single cell. II. There is a time and place for sex. PLoS Biol 8:e1000365
Narayana, Narendra; Weiss, Michael A (2009) Crystallographic analysis of a sex-specific enhancer element: sequence-dependent DNA structure, hydration, and dynamics. J Mol Biol 385:469-90
Yang, Yanwu; Zhang, Wei; Bayrer, James R et al. (2008) Doublesex and the regulation of sexual dimorphism in Drosophila melanogaster: structure, function, and mutagenesis of a female-specific domain. J Biol Chem 283:7280-92
Zhang, Wei; Li, Biaoru; Singh, Rupinder et al. (2006) Regulation of sexual dimorphism: mutational and chemogenetic analysis of the doublesex DM domain. Mol Cell Biol 26:535-47
Taylor, B J; Villella, A; Ryner, L C et al. (1994) Behavioral and neurobiological implications of sex-determining factors in Drosophila. Dev Genet 15:275-96
Baker, B S; Nagoshi, R N; Burtis, K C (1987) Molecular genetic aspects of sex determination in Drosophila. Bioessays 6:66-70