ARF1 Determines Asymmetric Cell Division in Oocyte Meiosis.

Abstract

Mouse oocyte undergoes two successive meiotic divisions and forms one large oocyte with two small polar bodies, which is essential for preserving the maternal complement of resources to support further embryonic development. Several small GTPase proteins, including Ran, Rac and Cdc42, have been found play important roles in meiotic spindle organization, anchoring and polar bodies extrusion. However, little is known about the mechanism of this extremely asymmetric cell division occurred in meiosis. Here we show that the ADP-ribosylation factor 1 (ARF1) is the determinant gene to drive the asymmetric cell division in oocyte meiosis. Microinjection of dominant negative isoform of ARF1 (ARF1T31N) mRNA into fully grown germinal vesicle oocytes led to symmetric cell division in meiosis I. Two metaphase II oocytes with equal size were generated from one single oocyte and arrested at M-phase. The similar phenomenon was observed in meiosis II, ARF1T31N expressed metaphase II oocytes underwent symmetric cell division when the oocytes were activated by either parthnogenetic activation or sperm injection. Furthermore, rotating of the metaphase spindle for 90 degree, which is essential for extruding small polar bodies, was prohibited in ARF1T31N mRNA injected oocytes, which might account for the symmetric cell division occurred in ARF1 mutant oocyte. Together, our results indicated that ARF1 plays critical role in determining asymmetric cell division in female meiosis. [Supported by National High Technology Project 863 (2005AA210930)]