IDENTIFICATION OF A DEVELOPMENTAL TIMER REGULATING THE STABILITY OF EMBRYONIC CYCLIN-A AND A NEW SOMATIC A-TYPE CYCLIN AT GASTRULATION

We have identified a second Xenopus cyclin A, called cyclin A2. Cyclin A2 is a 46.6-kD protein that shows a greater homology to human cyclin A than to the previously identified Xenopus cyclin A1. It is present throughout embryonic development (up to stage 46 at least) and is foun d in adult tissues as well as in Xenopus tissue culture cell lines. In contrast, cyclin A1 is present in eggs and early embryos but cannot b e detected in late embryos or in tissue culture cells. We have found t hat the maternally stared pools of mRNAs encoding both of these cyclin A proteins are stable until the onset of gastrulation and then are de graded abruptly. At this time, new transcription replaces cyclin A2 mR NA. Interestingly, we have also observed a dramatic change in the stab ility of the cyclin A proteins at this time. Prior to the onset of gas trulation, cyclin A1 protein is stable during interphase of the cell c ycle. At gastrulation, however, both A1 and A2 proteins turn over rapi dly during interphase of the cell cycle. Together, these results indic ate that developmental programs controlling cyclin A protein and mRNA stability are activated at gastrulation. We have shown that this progr am is independent of new transcription beginning at the mid-blastula t ransition. furthermore, treatment of early stage embryos with cyclohex imide demonstrates that activation of this degradative program is inde pendent of cell division and translation. Collectively, our observatio ns suggest that a previously uncharacterized timing mechanism activate s new degradative pathways at the onset of gastrulation, which could p lay an essential role in releasing cells from maternal programming.