Myt1 Kinase Couples Mitotic Cell Cycle Exit with Differentiation in Drosophila

The Drosophila midgut is an excellent system for characterizing cell cycle regulation in the context of tissue homeostasis. Two major progenitor cell types populate the midgut: mitotic intestinal stem cells and their post-mitotic daughters, enteroblasts. Although regulatory networks that control stem cell proliferation are well characterized, how enteroblast mitotic-cell-cycle exit is coordinated with endocycle entry and enterocyte specification remains poorly defined. Myt1 is a conserved Cdk1 inhibitory kinase that regulates mitotic timing during animal development. Here, we use myt1-null mutants and cell-specific RNA interference to investigate Myt1 function in stem cells and enteroblast progenitors. Myt1 depletion alters cell cycle kinetics and promotes ectopic stem cell and enteroblast mitoses at the expense of enteroblast-enterocyte differentiation. These aberrant enteroblast mitoses rely upon cyclin A, implicating Myt1 inhibition of cyclin A/Cdk1 as a mechanism for the coupling mitotic exit with differentiation in enteroblasts.