TY - JOUR
T1 - Notch promotes survival of neural precursor cells via mechanisms distinct from those regulating neurogenesis
AU - Oishi, Koji
AU - Kamakura, Sachiko
AU - Isazawa, Yuko
AU - Yoshimatsu, Takeshi
AU - Kuida, Keisuke
AU - Nakafuku, Masato
AU - Masuyama, Norihisa
AU - Gotoh, Yukiko
N1 - Funding Information:
This work was supported by Grants-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan, by PRESTO21 and CREST of the Japan Science and Technology Corporation and VRIA research foundation.
PY - 2004/12/1
Y1 - 2004/12/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ydbio.2004.08.039
DO - 10.1016/j.ydbio.2004.08.039
M3 - Article
C2 - 15531372
AN - SCOPUS:7544226214
VL - 276
SP - 172
EP - 184
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 1
ER -