Environmental control of the cell cycle in <i>Drosophila</i>: nutrition activates mitotic and endoreplicative cells by distinct mechanisms

TLDR

In newly hatched Drosophila larvae, quiescent cells reenter the cell cycle in response to dietary amino acids. The study varied larval nutrition to examine its effects on cell cycle initiation and maintenance in mitotic neuroblasts, imaginal disc cells, and endoreplicating cells. The authors monitored cell cycle initiation and maintenance in these cell types while manipulating larval nutrition. Mitotic cells continue proliferating independently of nutrition after activation, whereas most endoreplicating cells revert to quiescence; ectopic Cyclin E or E2F drives endoreplicating cells into S‑phase but not neuroblasts, and neuroblasts can be induced by fat‑body co‑culture, indicating distinct control mechanisms and a novel fat‑body‑derived mitogen.

Abstract

ABSTRACT In newly hatched Drosophila larvae, quiescent cells reenter the cell cycle in response to dietary amino acids. To understand this process, we varied larval nutrition and monitored effects on cell cycle initiation and maintenance in the mitotic neuroblasts and imaginal disc cells, as well as the endoreplicating cells in other larval tissues. After cell cycle activation, mitotic and endoreplicating cells respond differently to the withdrawal of nutrition: mitotic cells continue to proliferate in a nutrition-independent manner, while most endoreplicating cells reenter a quiescent state. We also show that ectopic expression of Drosophila Cyclin E or the E2F transcription factor can drive quiescent endoreplicating cells, but not quiescent imaginal neuroblasts, into S-phase. Conversely, we demonstrate that quiescent imaginal neuroblasts, but not quiescent endoreplicating cells, can be induced to enter the cell cycle when co-cultured with larval fat body in vitro. These results demonstrate a fundamental difference in the control of cell cycle activation and maintenance in these two cell types, and imply the existence of a novel mitogen generated by the larval fat body in response to nutrition.