The goal of the proposed experiments is to discover the mechanism by which the bag-of-marbles (bam) and benign gonial cell neoplasm (bgcn) gene products act to control the earliest steps in female germ cell differentiation from germ line stem cell precursors. Mutations in bam and bgcn have the same phenotype. Loss of function of either gene causes over proliferation of what appear to be primordial germ cells or germ line stem cells in females and over proliferation of interconnected, mitotically amplifying spermatogonia in males. Thus, in both sexes, Bam and Bgcn play a critical role in choices between proliferations as an undifferentiated precursor versus initiation of differentiation. The investigator proposes four aims to explore how Bam and Bgcn function. 1) To determine if the bam and bgcn proteins act together, the investigator will determine if bam and bgcn proteins co-localize in the cell or co-immunoprecipitate. 2) To investigate the mechanism of action of Bgcn and Bam, especially a possible role Bgcn in translational control, the investigator will screen for proteins that interact with Bgcn in the yeast two hybrid system and test if the Bgcn protein binds to RNA (as predicted based on its sequence homology). 3) To explore whether Bam protein function in the fusome is important for regulation of early germ cell differentiation, the investigator will identify the fusome targeting sequences in the Bam protein. If these can be eliminated without destroying Bam activity, it would argue against the investigator's model that localization of Bam protein to the fusome is important for its function in controlling germ cell fate. 4) To identify other components of the mechanism, the investigator will screen for mutations that enhance a weak bam mutant. In addition, the investigator will attempt to identify upstream regulations of bam using a screen for mutations that alter the cell type specific pattern of bam transcription or tiotranslantion.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM045820-13
Application #
6636027
Study Section
Special Emphasis Panel (ZRG1-MGN (01))
Program Officer
Greenberg, Judith H
Project Start
1991-05-01
Project End
2004-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
13
Fiscal Year
2003
Total Cost
$298,738
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Biochemistry
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Zhang, Qiao; Shalaby, Nevine A; Buszczak, Michael (2014) Changes in rRNA transcription influence proliferation and cell fate within a stem cell lineage. Science 343:298-301
Li, Yun; Zhang, Qiao; Carreira-Rosario, Arnaldo et al. (2013) Mei-p26 cooperates with Bam, Bgcn and Sxl to promote early germline development in the Drosophila ovary. PLoS One 8:e58301
Li, Yun; Maines, Jean Z; Tastan, Omur Y et al. (2012) Mei-P26 regulates the maintenance of ovarian germline stem cells by promoting BMP signaling. Development 139:1547-56
Tastan, Omur Y; Maines, Jean Z; Li, Yun et al. (2010) Drosophila ataxin 2-binding protein 1 marks an intermediate step in the molecular differentiation of female germline cysts. Development 137:3167-76
Insco, Megan L; Leon, Arlene; Tam, Cheuk Ho et al. (2009) Accumulation of a differentiation regulator specifies transit amplifying division number in an adult stem cell lineage. Proc Natl Acad Sci U S A 106:22311-6
Li, Yun; Minor, Nicole T; Park, Joseph K et al. (2009) Bam and Bgcn antagonize Nanos-dependent germ-line stem cell maintenance. Proc Natl Acad Sci U S A 106:9304-9
Maines, Jean Z; Park, Joseph K; Williams, Meredith et al. (2007) Stonewalling Drosophila stem cell differentiation by epigenetic controls. Development 134:1471-9
Liu, Xiang; Park, Joseph K; Jiang, Feng et al. (2007) Dicer-1, but not Loquacious, is critical for assembly of miRNA-induced silencing complexes. RNA 13:2324-9
Park, Joseph K; Liu, Xiang; Strauss, Tamara J et al. (2007) The miRNA pathway intrinsically controls self-renewal of Drosophila germline stem cells. Curr Biol 17:533-8
Chen, Dahua; McKearin, Dennis (2005) Gene circuitry controlling a stem cell niche. Curr Biol 15:179-84

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