Oscillations in notch signaling regulate maintenance of neural progenitors

Neuron
Hiromi ShimojoRyoichiro Kageyama

Abstract

Expression of the Notch effector gene Hes1 is required for maintenance of neural progenitors in the embryonic brain, but persistent and high levels of Hes1 expression inhibit proliferation and differentiation of these cells. Here, by using a real-time imaging method, we found that Hes1 expression dynamically oscillates in neural progenitors. Furthermore, sustained overexpression of Hes1 downregulates expression of proneural genes, Notch ligands, and cell cycle regulators, suggesting that their proper expression depends on Hes1 oscillation. Surprisingly, the proneural gene Neurogenin2 (Ngn2) and the Notch ligand Delta-like1 (Dll1) are also expressed in an oscillatory manner by neural progenitors, and inhibition of Notch signaling, a condition known to induce neuronal differentiation, leads to downregulation of Hes1 and sustained upregulation of Ngn2 and Dll1. These results suggest that Hes1 oscillation regulates Ngn2 and Dll1 oscillations, which in turn lead to maintenance of neural progenitors by mutual activation of Notch signaling.

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Citations

Sep 14, 2012·Cellular and Molecular Life Sciences : CMLS·Itaru ImayoshiRyoichiro Kageyama
Nov 15, 2011·Experimental Brain Research·Hidenori TabataKazunori Nakajima
Jul 19, 2011·Journal of Bone and Mineral Metabolism·Tadahiro IimuraAkira Yamaguchi
May 26, 2009·Molecules and Cells·Ryoichiro KageyamaHiromi Shimojo
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Apr 30, 2013·Neuropharmacology·Kazuyoshi KitaokaKazuo Yoshizaki
Jan 15, 2014·Progress in Retinal and Eye Research·Jenny R Lenkowski, Pamela A Raymond
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