Nek2 activation

Sexual reproduction requires the fusion of two haploid cells to form a diploid zygote. In higher eukaryotes, this implies that specialized diploid cells, the germ cells, reduce their chromosome content during meiosis. A single round of DNA replication followed by two cell divisions characterizes this process, such that a single diploid cell gives rise to four haploid cells. In the first division, homologs are initially held together by the synaptonemal complex, which dissolves at the end of the pachytene stage, and subsequently by chiasmata produced during homologous recombination (Roeder, 1997). At anaphase, sister chromatids do not separate and homologous chromosomes segregate to the opposite poles of the spindle into the two daughter cells (reviewed by Roeder, 1997; Handel and Eppig, 1998; Biggins and Murray, 1999). The second meiotic division resembles mitosis and sister chromatids are separated in the daughter cells to give rise to haploid spermatids (Handel and Eppig, 1998). Most of the knowledge on meiotic cell cycle events derives from studies performed on Xenopus oocytes, which are synchronized at the prophase of the first meiotic division and can be induced to progress through the cycle by stimulation with progesterone (reviewed by Sagata, 1997). The hormonal treatment leads to several biochemical changes that result in maturation of the oocyte: a decrease in cAMP-dependent protein kinase activity; the synthesis of the protein kinase Mos and activation of the MAPK pathway; activation of the Pololike-kinase (Plx1) pathway; dephosphorylation of Cdc2 by the dual specificity phosphatase Cdc25C; and the consequent activation of the CyclinB/Cdc2 complex, also known as maturation promoting factor (MPF) (Sagata et al., 1988; Sagata et al., 1989a; Sagata et al., 1989b; Qian et al., 1998; Qian et al., 2001). Although MPF activation and oocyte maturation can be obtained in vivo by microinjection of constitutively active forms of MAPKs (Gotoh et al., 1995; Haccard et al., 1995), recent evidence suggests that physiologically activation of the MAPK pathway is not sufficient for progression of oocytes through the first meiotic cycle. Indeed, inhibition of MAPKs by preincubation of oocytes with the specific MEK inhibitor 1715 Development 129, 1715-1727 (2002) Printed in Great Britain © The Company of Biologists Limited 2002 DEV3598