Notch promotes survival of neural precursor cells via mechanisms distinct from those regulating neurogenesis

Koji Oishi, Sachiko Kamakura, Yuko Isazawa, Takeshi Yoshimatsu, Keisuke Kuida, Masato Nakafuku, Norihisa Masuyama, Yukiko Gotoh

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)

Abstract

During development of the mammalian brain, many neural precursor cells (NPCs) undergo apoptosis. The regulation of such cell death, however, is poorly understood. We now show that the survival of mouse embryonic NPCs in vitro was increased by culture at a high cell density and that this effect was attributable to activation of Notch signaling. Expression of an active form of Notch1 thus markedly promoted NPC survival. Hes proteins, key effectors of Notch signaling in inhibition of neurogenesis, were not sufficient for the survival-promoting effect of Notch1. This effect of Notch1 required a region of the protein containing the RAM domain and was accompanied by up-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1. Moreover, knockdown of these proteins by RNA interference resulted in blockade of the Notch1-induced survival. These results reveal a new function of Notch, the promotion of NPC survival.

Original languageEnglish
Pages (from-to)172-184
Number of pages13
JournalDevelopmental Biology
Volume276
Issue number1
DOIs
Publication statusPublished - Dec 1 2004

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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