In this new application, the applicant proposes to examine events leading to testis development. The working hypothesis is that testicular development starts immediately after the expression of the Sry gene. Therefore, Sry initiates multiple signaling pathways including those related to direct cell migration, cell-cell interaction and proliferation required for the divergence of the indifferent gonad into testicular organogenesis. Studies include the use of novel in vivo and organ culture methods to define differences in patterns of cell proliferation and migration downstream Sry expression. Two major specific aims are proposed.
Specific Aim 1 will examine cell types contributed by proliferation and migration and the importance of these mechanisms to the development of testis cords in male gonads.
Specific Aim 2 will examine candidate signaling molecules required for the migratory and differentiating cells. The effect of these molecules will be examined by assaying for differential activation between male and female responsive cells, their ability to induce male-specific patterns in a female gonad in culture, and by blocking specific responses in culture assays to test the effects on migration, proliferation or cord formation in male gonads. Null mutants that fail to express specific factors and receptors will be examined to determine phenotypic consequences of genetic interference with migratory or proliferation signals.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM056757-02
Application #
2857321
Study Section
Reproductive Biology Study Section (REB)
Project Start
1998-01-01
Project End
2000-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Duke University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
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Cui, Shiying; Ross, Andrea; Stallings, Nancy et al. (2004) Disrupted gonadogenesis and male-to-female sex reversal in Pod1 knockout mice. Development 131:4095-105
Yao, Humphrey H-C; DiNapoli, Leo; Capel, Blanche (2003) Meiotic germ cells antagonize mesonephric cell migration and testis cord formation in mouse gonads. Development 130:5895-902
Yao, Humphrey Hung-Chang; Tilmann, Christopher; Zhao, Guang-Quan et al. (2002) The battle of the sexes: opposing pathways in sex determination. Novartis Found Symp 244:187-98; discussion 198-206, 253
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Schmahl, J; Eicher, E M; Washburn, L L et al. (2000) Sry induces cell proliferation in the mouse gonad. Development 127:65-73
Tilmann, C; Capel, B (1999) Mesonephric cell migration induces testis cord formation and Sertoli cell differentiation in the mammalian gonad. Development 126:2883-90