This ongoing project is concerned with the signalling mechanisms by which fertilization causes an egg to begin development. The project is focused on the earliest events of this process, which occur at the egg plasma membrane. These membrane events cause a rise in intracellular Ca2+, which in turn causes many subsequent developmental processes. Ca2+ release at fertilization occurs as a consequence of the action of the phospholipase C family of enzymes, which produce inositol 1,4,5- trisphosphate (IP3) from the membrane lipid phosphatidylinositol 4,5- bisphosphate (PIP2); PIP2 itself is produced by PIP kinases. Recent studies have shown that in echinoderm eggs, Ca2+ release is initiated by a signalling pathway involving the sequential activation of a Src family kinase and phospholipase C-gamma. In mammalian fertilization, the sequence of events leading to IP3 production is unknown. We propose to investigate the signalling mechanisms by which a Src family kinase is activated at fertilization of echinoderm eggs, and to investigate the possible roles of Src family kinases and PIP kinases in the signalling pathway leading to Ca2+ release at fertilization of mammalian eggs. The long term objective of these studies is to understand how the earliest events of sperm-egg interaction result in egg activation at fertilization. The significance of this work to the study of human reproduction is in providing the basic science background that underlies clinical advances.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Tasca, Richard J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Connecticut
Anatomy/Cell Biology
Schools of Medicine
United States
Zip Code
Lee, Kyung-Bon; Zhang, Meijia; Sugiura, Koji et al. (2013) Hormonal coordination of natriuretic peptide type C and natriuretic peptide receptor 3 expression in mouse granulosa cells. Biol Reprod 88:42
Robinson, Jerid W; Zhang, Meijia; Shuhaibar, Leia C et al. (2012) Luteinizing hormone reduces the activity of the NPR2 guanylyl cyclase in mouse ovarian follicles, contributing to the cyclic GMP decrease that promotes resumption of meiosis in oocytes. Dev Biol 366:308-16
Norris, Rachael P; Freudzon, Marina; Nikolaev, Viacheslav O et al. (2010) Epidermal growth factor receptor kinase activity is required for gap junction closure and for part of the decrease in ovarian follicle cGMP in response to LH. Reproduction 140:655-62
Norris, Rachael P; Ratzan, William J; Freudzon, Marina et al. (2009) Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte. Development 136:1869-78
Jaffe, Laurinda A; Norris, Rachael P; Freudzon, Marina et al. (2009) Microinjection of follicle-enclosed mouse oocytes. Methods Mol Biol 518:157-73
Norris, Rachael P; Freudzon, Marina; Mehlmann, Lisa M et al. (2008) Luteinizing hormone causes MAP kinase-dependent phosphorylation and closure of connexin 43 gap junctions in mouse ovarian follicles: one of two paths to meiotic resumption. Development 135:3229-38
Norris, Rachael P; Freudzon, Leon; Freudzon, Marina et al. (2007) A G(s)-linked receptor maintains meiotic arrest in mouse oocytes, but luteinizing hormone does not cause meiotic resumption by terminating receptor-G(s) signaling. Dev Biol 310:240-9
Mehlmann, Lisa M; Kalinowski, Rebecca R; Ross, Lavinia F et al. (2006) Meiotic resumption in response to luteinizing hormone is independent of a Gi family G protein or calcium in the mouse oocyte. Dev Biol 299:345-55
Mehlmann, Lisa M; Jaffe, Laurinda A (2005) SH2 domain-mediated activation of an SRC family kinase is not required to initiate Ca2+ release at fertilization in mouse eggs. Reproduction 129:557-64
Mehlmann, Lisa M (2005) Oocyte-specific expression of Gpr3 is required for the maintenance of meiotic arrest in mouse oocytes. Dev Biol 288:397-404

Showing the most recent 10 out of 39 publications