Cyclin E and Cdk1 regulate the termination of germline transit-amplification process in testis.

An extension of the G1 is correlated with stem cell differentiation. The role of cell cycle regulation during the subsequent transit amplification (TA) divisions is, however, unclear. Here, we report for the first time that in the male germline lineage, the transit amplification divisions accelerate after the second TA division. The cell cycle phases, marked by Cyclin E and Cyclin B, are progressively altered during the TA. Antagonistic functions of the and the Transforming-Growth-Factor-β signaling regulate the cell division rates after the second TA division and the extent of the Cyclin E phase during the fourth TA division. Furthermore, loss of Cyclin E during the fourth TA cycle retards the cell division and induces premature meiosis in some cases. A similar reduction of Cdk1 activity during this stage arrests the penultimate division and subsequent differentiation, whereas enhancement of the Cdk1 activity prolongs the TA by one extra round. Altogether, the results suggest that modification of the cell cycle structure and the rates of cell division after the second TA division determine the extent of amplification. Also, the regulation of the Cyclin E and CDK1 functions during the penultimate TA division determines the induction of meiosis and subsequent differentiation.