Gerhold, A. R.; Cheng, E.; Lu, R.

Stem and progenitor cell mitosis is essential for tissue development and homeostasis. How these cells ensure proper chromosome segregation, and thereby maintain mitotic fidelity, in the complex physiological environment of a living animal is poorly understood. Here we use in situ live-cell imaging of C. elegans germline stem and progenitor cells (GSPCs) to ask whether signaling pathways that play a conserved role in regulating stem and progenitor cell cycle progression also impact mitosis. Through a candidate screen we identify a new role for the insulin/IGF receptor (IGFR), daf-2, as a regulator of GSPC mitosis. Mitosis is delayed in daf-2/IGFR mutants, and these delays require canonical, DAF-2/IGFR to DAF-16/FoxO insulin signaling, here acting cell non-autonomously from the soma. We further show that while mitotic delays in daf-2/IGFR mutants depend on the spindle assembly checkpoint, they are not accompanied by a loss of mitotic fidelity. Finally, we show that caloric restriction, which delays GSPC mitosis and compromises mitotic fidelity, does not act via the canonical insulin signaling pathway, and instead requires AMP-activated kinase (AMPK). Together this work demonstrates that GSPC mitosis is regulated by at least two genetically separable signaling pathways and highlights the importance of signaling networks for proper stem and progenitor cell mitosis in vivo.