Start of the embryonic cell cycle is dually locked in unfertilized starfish eggs.

A key event in the oocyte-to-embryo transition is the start of the embryonic mitotic cell cycle. Prior to this start, the cell cycle in oocytes is generally arrested at a particular stage during meiosis, and the meiotic arrest is released by fertilization. However, it remains unclear how release from the meiotic arrest is implicated in the start of the embryonic cell cycle. To elucidate this link, we have used starfish eggs, in which G1 phase arrest occurs after completion of meiosis if the mature oocytes are not fertilized, and fertilization simply directs the start of the embryonic cell cycle. The starfish G1 arrest is known to rely on the Mos-MAPK-Rsk (p90 ribosomal S6 kinase) pathway, and inactivation of Rsk induces S phase in the absence of fertilization. However, here we show that this S phase is not followed by M phase when MAPK remains active, owing to poly(A)-independent repression of cyclin A and B synthesis. By contrast, inactivation of MAPK alone induces M phase, even when S phase is inhibited by constitutively active Rsk. Thus, there is a divergence of separate pathways downstream of MAPK that together block the start of the embryonic mitotic cycle. One is the previously known Rsk-dependent pathway that prevents S phase, and the other is a novel pathway that is not mediated by Rsk and that leads to prevention of the first mitotic M phase through suppression of protein synthesis of M phase cyclins. Release from such a 'dual-lock' by fertilization results in the start of the embryonic cell cycle.