Myt1 Kinase Couples Mitotic Cell Cycle Exit with Differentiation in  <i>Drosophila</i>

Abstract

Inhibitory phosphorylation of Cdk1 is a well-established mechanism for gating mitotic entry during development. However, failure to inhibit Cdk1 in adult organs causes ectopic cell division and tissue dysplasia, indicating that Cdk1 inhibition is also required for cell cycle exit. Two types of progenitor cells populate the adult Drosophila midgut: intestinal stem cells (ISCs) and post-mitotic enteroblasts (EBs). ISCs are the only mitotic cells under homeostatic conditions, dividing asymmetrically to produce quiescent EB daughter cells. We show here that Myt1, the membrane associated Cdk1 inhibitory kinase, is required for EB quiescence and subsequent differentiation. Loss of Myt1 disrupts EB cell cycle dynamics, promoting Cyclin A-dependent mitosis and accumulation of smaller progenitor-like cells that fail to differentiate. Thus, Myt1 inhibition of Cyclin A/Cdk1 functions as a mechanism for coupling cell cycle arrest with terminal cell differentiation in this developmental context.