The sex determination mechanisms responsible for creating sexual dimorphism are diverse throughout the animal kingdom, such as cell autonomous splicing of specific sex factors in flies and hormonal secretion by gonads in humans, but converge upon a family of conserved genes, Dmrt's (dsx, mab-3 related transcription factors), that encode products that regulate sex specific gene expression. The Dmrt family of transcription factors share a common DNA-binding domain (DM domain), are expressed tissue specifically, and instruct those cells of the tissue they are expressed in to follow along a female or male developmental program. Moreover, chromosomal deletions affecting Dmrt's has been linked to a human syndrome of sex reversal. While the mechanisms by which sexual identity leads to sex-specific control of development are still being elucidated, the role of Dmrt's is most understood in Drosophila. The founding member of the Dmrt family, doublesex (dsx), was identified as a mutation affecting sexual differentiation resulting in an intersexual phenotype between males and females in Drosophila. In Drosophila, nearly all manifestations of sexual dimorphism are regulated by the presence of sex-specific transcripts, doublesex (dsx) and fruitless (fru), generated at the end of the sex determination cascade. Though this pathway has been established for many years, few direct targets for the DSX transcription factors are known. Direct targets of DSX include the yolk protein genes expressed in female fat body which encode yolk protein that get deposited in the oocytes;the bric-a-brac locus (bab1 and bab2) which encode transcription factors that regulate the presence sex-specific abdominal pigmentation;and desaturase-F which encodes a protein involved in female specific pheromone synthesis. Since interaction between DSX and its three known targets cannot account for the differences in regulation by DSX in all sexually dimorphic tissues it is expressed in, it is of great importance to identify direct and transcriptionally regulated targets f DSX.

Public Health Relevance

Specific characteristics are those traits that distinguish one sex from another, morphologically and behaviorally. The sex determination mechanisms responsible for creating sex-specific traits are diverse throughout the animal kingdom. Studies on human infertility have illustrated that defects in the sex- determination pathway lean to intersexual gonads, physical abnormalities, and sterility. The proposed research seeks to elucidate the mechanism by which sexual identity leads to sex-specific characteristics.

Agency
National Institute of Health (NIH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31HD076558-02
Application #
8655457
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Taymans, Susan
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21218