The generation of oocytes is a complex process that begins in early embryogenesis and which culminates in the adult with the fertilization and subsequent development of a new organism. The developmental program of the oocyte requires that it expresses genes not only for its own development, but also that of the early embryo prior to zygotic genome activation. The latter process requires the storage of maternal RNAs. Recently, a novel germ cell specific gene of unknown function, called tudor domain containing 1 (TDRD1), has been cloned. Tudor domain containing proteins have been implicated in the regulation of RNA storage and metabolism, and similarly, TDRD1 may be involved in the regulation of oocyte mRNAs. The long-term objective of this proposal is to characterize this germ cell specific gene.
The specific aims of this proposal are to 1) fully identify and characterize the expression of Tdrd1 in early embryonic, fetal, and adult stages of oogenesis; 2) analyze the function of TDRD1 in oogenesis by identifying the proteins with which it interacts; and 3) generate a mouse knockout model of TDRD1 in order to test the in vivo role of TDRD1 in male and female fertility. These studies will potentially lead to an understanding TDRD1 function in germ cell development, and in turn, of the process of oogenesis. A better understanding of oogenesis is necessary as we try to develop more successful treatments for human infertility.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HD046335-03
Application #
7108661
Study Section
Special Emphasis Panel (ZRG1-F06 (20))
Program Officer
Taymans, Susan
Project Start
2004-09-01
Project End
2007-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
3
Fiscal Year
2006
Total Cost
$52,048
Indirect Cost
Name
Baylor College of Medicine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Su, You-Qiang; Sugiura, Koji; Wigglesworth, Karen et al. (2008) Oocyte regulation of metabolic cooperativity between mouse cumulus cells and oocytes: BMP15 and GDF9 control cholesterol biosynthesis in cumulus cells. Development 135:111-21
Pangas, Stephanie A; Li, Xiaohui; Umans, Lieve et al. (2008) Conditional deletion of Smad1 and Smad5 in somatic cells of male and female gonads leads to metastatic tumor development in mice. Mol Cell Biol 28:248-57
Sugiura, Koji; Su, You-Qiang; Diaz, Francisco J et al. (2007) Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells. Development 134:2593-603
Pangas, Stephanie A; Jorgez, Carolina J; Tran, Mai et al. (2007) Intraovarian activins are required for female fertility. Mol Endocrinol 21:2458-71
Pangas, Stephanie A (2007) Growth factors in ovarian development. Semin Reprod Med 25:225-34
Ballow, Daniel J; Xin, Yun; Choi, Youngsok et al. (2006) Sohlh2 is a germ cell-specific bHLH transcription factor. Gene Expr Patterns 6:1014-8
Pangas, Stephanie A; Choi, Youngsok; Ballow, Daniel J et al. (2006) Oogenesis requires germ cell-specific transcriptional regulators Sohlh1 and Lhx8. Proc Natl Acad Sci U S A 103:8090-5
Pangas, Stephanie A; Rajkovic, Aleksandar (2006) Transcriptional regulation of early oogenesis: in search of masters. Hum Reprod Update 12:65-76
Pangas, Stephanie A; Li, Xiaohui; Robertson, Elizabeth J et al. (2006) Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice. Mol Endocrinol 20:1406-22
Pangas, Stephanie A; Matzuk, Martin M (2005) The art and artifact of GDF9 activity: cumulus expansion and the cumulus expansion-enabling factor. Biol Reprod 73:582-5

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