The overall goal of the proposed research is investigation of the potential roles of proto-oncogenes in mammalian gametogenesis and early embryonic development. The c-mos c-abi and int-1 proto-oncogenes are transcribed during specific stages of spermatogenesis in the mouse. In addition, c-mos is transcribed in growing oocytes and high levels of c- mos RNA are accumulated by the germinal vesicle stage. The oocyte c-mos RNA is post-transcriptionally polyadenylated in concert with oocyte maturation and is degraded by the mid to late two cell stage, suggesting possible roles for c-mos as a maternal message. Since c-mos represents the first candidate for a regulatory maternal RNA unique to oocytes, further studies with its expression in spermatogenesis. Synthesis, phosphorylation and stability of the c-mos protein will be studied in spermatocytes, oocytes, eggs and embryos. The biological functions of c- mos in oocytes will be investigated by inhibiting c-mos expression using anti-sense oligonucleotides and/or anti-mos antibodies. These studies will be correlated with alterations in protein phosphorylation to identify candidate targets for c-mos protein kinase activity. Regulatory sequences and trans-acting factors which control c-mos expression during maturation of spermatocytes and oocytes will be investigated and the developmental specificity of c-mos expression in spermatogenesis will be further studied. The expression of additional selected proto-oncogenes will be studied in spermatogenesis, oogenesis and pre-implantation mouse embryos. These studies of normal proto-oncogene function in development will also contribute to understanding the mechanisms by which oncogenes induce neoplastic transformation.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Molecular Cytology Study Section (CTY)
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Dana-Farber Cancer Institute
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Gross, Vera S; Hess, Mailee; Cooper, Geoffrey M (2005) Mouse embryonic stem cells and preimplantation embryos require signaling through the phosphatidylinositol 3-kinase pathway to suppress apoptosis. Mol Reprod Dev 70:324-32
Zilz, Alexandra; Cooper, Geoffrey M (2004) A binding site for germ cell nuclear factor within c-mos regulatory sequences. Mol Reprod Dev 67:55-64
Gross, Vera S; Cooper, Geoffrey M (2002) Functional analysis of sperm from c-mos(-/-) mice. Mol Reprod Dev 62:519-24
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Xu, W; Cooper, G M (1995) Identification of a candidate c-mos repressor that restricts transcription of germ cell-specific genes. Mol Cell Biol 15:5369-75
Pal, S K; Torry, D; Serta, R et al. (1994) Expression and potential function of the c-mos proto-oncogene in human eggs. Fertil Steril 61:496-503
Gebauer, F; Xu, W; Cooper, G M et al. (1994) Translational control by cytoplasmic polyadenylation of c-mos mRNA is necessary for oocyte maturation in the mouse. EMBO J 13:5712-20
Yamauchi, N; Kiessling, A A; Cooper, G M (1994) The Ras/Raf signaling pathway is required for progression of mouse embryos through the two-cell stage. Mol Cell Biol 14:6655-62
Pal, S K; Crowell, R; Kiessling, A A et al. (1993) Expression of proto-oncogenes in mouse eggs and preimplantation embryos. Mol Reprod Dev 35:8-15
Zinkel, S S; Pal, S K; Szeberenyi, J et al. (1992) Identification of a negative regulatory element that inhibits c-mos transcription in somatic cells. Mol Cell Biol 12:2029-36

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