SRC-FAMILY TYROSINE KINASES PARTICIPATE IN THE REGULATION OF MAMMALIAN OOCYTE MATURATION AND ZYGOTIC DEVELOPMENT

Abstract

Multiple signaling pathways act during ovulation to ensure that the oocyte is prepared for embryonic development. We combined pharmacological and cell biological methods to study the role of Src-family kinases (SFKs) during oocyte maturation, fertilization and embryonic cleavage in mice. Active SFKs localize to spindle microtubules and the cell cortex. Fyn kinase is the primary SFK in mouse oocytes. Disruption of Fyn kinase causes abnormalities in chromatin separation and spindle formation. Site specific tyrosine phosphorylation events in the egg cortex near chromatin are altered by the conditions under which oocyte in vitro maturation occurs. Thus, previously unanticipated functions for SFKs are identified that mediate spatial and temporal remodeling of cytoskeleton and cell cycle during oocyte maturation and early development. These findings bear directly on human assisted reproductive technology with the discovery of the role of this pathway in maturation and embryonic cleavage of mammalian oocytes.