Fully-grown Xenopus laevis oocytes are arrested in a G2-like state, with inactive Cdc2 and an intact nucleus or germinal vesicle. In response to environmental cues in vivo, or progesterone ex vivo, oocytes are induced to mature. During maturation they activate their Cdc2, undergo germinal vesicle breakdown, complete the first meiotic division, enter meiosis 2, and then finally arrest in metaphase of meiosis 2. Work over the past few years has established that the all-or-none activation of the MAPK cascade triggers the activation of Cdc2/cyclin B during Xenopus oocyte maturation. Important unanswered questions include how the all-or-none behavior of the MAPK cascade arises, how the activation of the MAPK cascade is initiated, and what links the activation of MAPK to the activation of Cdc2. The present proposal aims to answer these questions. The hope is to gain insight into the process of oocyte maturation; the mechanisms of Cdc2/cyclin B regulation; and the dynamical behavior of the MAPK cascade. There are four Specific Aims: 1. How is the MAPK cascade's switch-like response generated, and how general is this phenomenon? 2. What initiates activation of the MAPK cascade in vivo? 3. How does the MAPK cascade bring about Cdc2 activation? 4. How does activation of the MAPK cascade bring about G2 arrest in cycling extracts and embryos, and what is the significance of this arrest?
Showing the most recent 10 out of 33 publications
