TY - JOUR
T1 - Prdm16 is crucial for progression of the multipolar phase during neural differentiation of the developing neocortex
AU - Inoue, Mayuko
AU - Iwai, Ryota
AU - Tabata, Hidenori
AU - Konno, Daijiro
AU - Komabayashi-Suzuki, Mariko
AU - Watanabe, Chisato
AU - Iwanari, Hiroko
AU - Mochizuki, Yasuhiro
AU - Hamakubo, Takao
AU - Matsuzaki, Fumio
AU - Nagata, Koh Ichi
AU - Mizutani, Ken Ichi
N1 - Funding Information:
This research was supported by Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology (PRESTO) ?Development and Function of Neural Networks? (111832), by a Grant-in-Aid for Scientific Research on Innovative Areas ?Neurovascular? from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (25122718) and by the Takeda Science Foundation.
Publisher Copyright:
© 2017. Published by The Company of Biologists Ltd.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - The precise control of neuronal migration and morphological changes during differentiation is essential for neocortical development. We hypothesized that the transition of progenitors through progressive stages of differentiation involves dynamic changes in levels of mitochondrial reactive oxygen species (mtROS), depending on cell requirements.We found that progenitors had higher levels of mtROS, but that these levels were significantly decreased with differentiation. The Prdm16 gene was identified as a candidate modulator of mtROS using microarray analysis, and was specifically expressed by progenitors in the ventricular zone. However, Prdm16 expression declined during the transition into NeuroD1-positive multipolar cells. Subsequently, repression of Prdm16 expression by NeuroD1 on the periphery of ventricular zone was crucial for appropriate progression of the multipolar phase and was required for normal cellular development. Furthermore, time-lapse imaging experiments revealed abnormal migration and morphological changes in Prdm16-overexpressing and -knockdown cells. Reporter assays and mtROS determinations demonstrated that PGC1α is a major downstream effector of Prdm16 and NeuroD1, and is required for regulation of the multipolar phase and characteristic modes of migration. Taken together, these data suggest that Prdm16 plays an important role in dynamic cellular redox changes in developing neocortex during neural differentiation.
AB - The precise control of neuronal migration and morphological changes during differentiation is essential for neocortical development. We hypothesized that the transition of progenitors through progressive stages of differentiation involves dynamic changes in levels of mitochondrial reactive oxygen species (mtROS), depending on cell requirements.We found that progenitors had higher levels of mtROS, but that these levels were significantly decreased with differentiation. The Prdm16 gene was identified as a candidate modulator of mtROS using microarray analysis, and was specifically expressed by progenitors in the ventricular zone. However, Prdm16 expression declined during the transition into NeuroD1-positive multipolar cells. Subsequently, repression of Prdm16 expression by NeuroD1 on the periphery of ventricular zone was crucial for appropriate progression of the multipolar phase and was required for normal cellular development. Furthermore, time-lapse imaging experiments revealed abnormal migration and morphological changes in Prdm16-overexpressing and -knockdown cells. Reporter assays and mtROS determinations demonstrated that PGC1α is a major downstream effector of Prdm16 and NeuroD1, and is required for regulation of the multipolar phase and characteristic modes of migration. Taken together, these data suggest that Prdm16 plays an important role in dynamic cellular redox changes in developing neocortex during neural differentiation.
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U2 - 10.1242/dev.136382
DO - 10.1242/dev.136382
M3 - Article
C2 - 27993981
AN - SCOPUS:85011582870
VL - 144
SP - 385
EP - 399
JO - Journal of Embryology and Experimental Morphology
JF - Journal of Embryology and Experimental Morphology
SN - 0950-1991
IS - 3
ER -