A novel role for glycogen synthase kinase-3 in Xenopus development: maintenance of oocyte cell cycle arrest by a beta-catenin-independent mechanism

We have examined the expression of glycogen synthase kinase-3 beta in oocyt es and early embryos of Xenopus and found that the protein is developmental ly regulated. In resting oocytes, GSK-3 beta is active and it is inactivate d on maturation in response to progesterone. GSK-3 beta inactivation is nec essary and rate limiting for the cell cycle response to this hormone and th e subsequent accumulation of beta-catenin. Overexpression of a dominant neg ative form of the kinase accelerates maturation, as does inactivation by ex pression of Xenopus Dishevelled or microinjection of an inactivating antibo dy. Cell cycle inhibition by GSK-3 beta is not mediated by the level of bet a-catenin or by a direct effect on either the MAP kinase pathway or transla tion of mos and cyclin B1. These data indicate a novel role for GSK-3 beta in Xenopus development: in addition to controlling specification of the dor soventral axis in embryos, it mediates cell cycle arrest in oocytes.