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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD026594-01
Application #
3328084
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1989-08-01
Project End
1994-04-30
Budget Start
1989-08-01
Budget End
1990-04-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
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
Lin, H B; Jurk, M; Gulick, T et al. (1999) Identification of COUP-TF as a transcriptional repressor of the c-mos proto-oncogene. J Biol Chem 274:36796-800
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

Showing the most recent 10 out of 12 publications