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First published online November 11, 2009
doi: 10.1242/10.1242/dev.039180

Development 136, 3889-3893 (2009)
Published by The Company of Biologists 2009
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Identification of Nepro, a gene required for the maintenance of neocortex neural progenitor cells downstream of Notch

Yuko Muroyama and Tetsuichiro Saito*

Department of Developmental Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan

* Author for correspondence (tesaito{at}faculty.chiba-u.jp)

Accepted September 21, 2009

In the developing neocortex, neural progenitor cells (NPCs) produce projection neurons of the six cortical layers in a temporal order. Over the course of cortical neurogenesis, maintenance of NPCs is essential for the generation of distinct types of neurons at the required time. Notch signaling plays a pivotal role in the maintenance of NPCs by inhibiting neuronal differentiation. Although Hairy and Enhancer-of-split (Hes)-type proteins are central to Notch signaling, it remains unclear whether other essential effectors take part in the pathway. In this study, we identify Nepro, a gene expressed in the developing mouse neocortex at early stages that encodes a 63 kDa protein that has no known structural motif except a nuclear localization signal. Misexpression of Nepro inhibits neuronal differentiation only in the early neocortex. Furthermore, knockdown of Nepro by siRNA causes precocious differentiation of neurons. Expression of Nepro is activated by the constitutively active form of Notch but not by Hes genes. Nepro represses expression of proneural genes without affecting the expression of Hes genes. Finally, we show that the combination of Nepro and Hes maintains NPCs even when Notch signaling is blocked. These results indicate that Nepro is involved in the maintenance of NPCs in the early neocortex downstream of Notch.

Key words: Neural progenitor cell, Cerebral cortex, Notch, Mouse


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