TY - JOUR
T1 - Clock genes regulate neurogenic transcription factors, including NeuroD1, and the neuronal differentiation of adult neural stem/progenitor cells
AU - Kimiwada, Tomomi
AU - Sakurai, Mikako
AU - Ohashi, Hiroki
AU - Aoki, Shunsuke
AU - Tominaga, Teiji
AU - Wada, Keiji
N1 - Funding Information:
This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Health, Labour and Welfare of Japan, Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation, and a grant from the Japan Science and Technology Agency.
PY - 2009/5
Y1 - 2009/5
N2 - The circadian clock system plays multiple roles in our bodies, and clock genes are expressed in various brain regions, including the lateral subventricular zone (SVZ) where neural stem/progenitor cells (NSPCs) persist and postnatal neurogenesis continues. However, the functions of clock genes in adult NSPCs are not well understood. Here, we first investigated the expression patterns of Clock and Bmal1 in the SVZ by immunohistochemistry and then verified how the expression levels of 17 clock and clock-related genes changed during differentiation of cultured adult NSPCs using quantitative RT-PCR. Finally, we used RNAi to observe the effects of Clock and Bmal1 on neuronal differentiation. Our results revealed that Clock and Bmal1 were expressed in the SVZ and double-stained with the neural progenitor marker Nestin and neural stem marker GFAP. In cultured adult NSPCs, the clock genes changed their expression patterns during differentiation, and interestingly, Bmal1 started endogenous oscillation. Moreover, gene silencing of Clock or Bmal1 by RNAi decreased the percentages of neuronal marker Map2-positive cells and expression levels of NeuroD1 mRNA. These findings suggest that clock genes are involved in the neuronal differentiation of adult NSPCs and may extend our understanding of various neurological/psychological disorders linked to adult neurogenesis and circadian rhythm.
AB - The circadian clock system plays multiple roles in our bodies, and clock genes are expressed in various brain regions, including the lateral subventricular zone (SVZ) where neural stem/progenitor cells (NSPCs) persist and postnatal neurogenesis continues. However, the functions of clock genes in adult NSPCs are not well understood. Here, we first investigated the expression patterns of Clock and Bmal1 in the SVZ by immunohistochemistry and then verified how the expression levels of 17 clock and clock-related genes changed during differentiation of cultured adult NSPCs using quantitative RT-PCR. Finally, we used RNAi to observe the effects of Clock and Bmal1 on neuronal differentiation. Our results revealed that Clock and Bmal1 were expressed in the SVZ and double-stained with the neural progenitor marker Nestin and neural stem marker GFAP. In cultured adult NSPCs, the clock genes changed their expression patterns during differentiation, and interestingly, Bmal1 started endogenous oscillation. Moreover, gene silencing of Clock or Bmal1 by RNAi decreased the percentages of neuronal marker Map2-positive cells and expression levels of NeuroD1 mRNA. These findings suggest that clock genes are involved in the neuronal differentiation of adult NSPCs and may extend our understanding of various neurological/psychological disorders linked to adult neurogenesis and circadian rhythm.
KW - Adult neural stem/progenitor cell
KW - Adult neurogenesis
KW - Bmal1
KW - Circadian rhythm
KW - Clock
KW - NeuroD1
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UR - http://www.scopus.com/inward/citedby.url?scp=61449225444&partnerID=8YFLogxK
U2 - 10.1016/j.neuint.2008.12.005
DO - 10.1016/j.neuint.2008.12.005
M3 - Article
C2 - 19121353
AN - SCOPUS:61449225444
VL - 54
SP - 277
EP - 285
JO - Neurochemistry International
JF - Neurochemistry International
SN - 0197-0186
IS - 5-6
ER -