Prdm16 is crucial for progression of the multipolar phase during neural differentiation of the developing neocortex

Mayuko Inoue, Ryota Iwai, Hidenori Tabata, Daijiro Konno, Mariko Komabayashi-Suzuki, Chisato Watanabe, Hiroko Iwanari, Yasuhiro Mochizuki, Takao Hamakubo, Fumio Matsuzaki, Koh Ichi Nagata, Ken Ichi Mizutani

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)385-399
Number of pages15
JournalDevelopment (Cambridge)
Volume144
Issue number3
DOIs
Publication statusPublished - Feb 1 2017
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Cite this