ABSTRACT

Embryonic neural stem cells(NSCs) give rise to various types of neurons, initially deep-layer neurons and then upper-layer neurons, and fi nally differentiate into astrocytes. During this process, NSCs switch their differentiation competency by changing gene expression profi les regulated by transcription factors. In these cells, expression of the Notch effector Hes1, a transcriptional repressor, oscillates with a period of 2-3 hours and Hes1 oscillations drive the oscillatory expression of the proneural gene Neurogenin2 (Ngn2) and the Notch ligand gene Delta-like1 (Dll1). Dll1 oscillation leads to the mutual activation of Notch signaling between neighboring cells. After Hes1 expression is repressed, Ngn2 is expressed in a sustained manner, promoting neuronal differentiation. Thus, Ngn2 leads

1Institute for Virus Research, Kyoto University. 2Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST). 3The Hakubi Center, Kyoto University. 4Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology (PRESTO), Kyoto 606-8507, Japan. Corresponding author: rkageyam@virus.kyoto-u.ac.jp

List of abbreviations after the text.