Krüppel-like factor 4 and 5 oppositely determine neural precursor cell fate in the developing mammalian brain

Krüppel-like factors (Klfs) are DNA-binding transcriptional factors and regulate multiple physiological features including cell cycle regulation, cell differentiation and tissue organization. Klf2, Klf4 and Klf5 are crucial for the maintenance of pluripotent and somatic stem cells. Here, we show that Klf2, Klf4 and Klf5 are required for the normal neural development in a redundant manner and that depletion of all three genes in neural precursor cells results in impaired activation of Notch signaling and early lethality. Klf5 plays a dominant role in the maintenance of neural precursor cell population by suppressing their differentiation and radial migration in the mammalian developing brain. In addition, Klf4 and Klf5 regulate the proliferation of neural precursor cells in opposite directions. Our findings provide new insight on how neural precursor cells are preserved to provide both large number of differentiating cells and a few quiescent neural stem cells.