Prdm16 is critical for progression of the multipolar phase during neural differentiation of the developing neocortex
| Autor: | Daijiro Konno, Fumio Matsuzaki, Takao Hamakubo, Mayuko Inoue, Ken Ichi Mizutani, Ryota Iwai, Chisato Watanabe, Hiroko Iwanari, Yasuhiro Mochizuki, Mariko Komabayashi-Suzuki, Hidenori Tabata, Koh-ichi Nagata |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Neurogenesis Cellular differentiation Mice Transgenic Neocortex Biology Time-Lapse Imaging Mice 03 medical and health sciences Neural Stem Cells Cell Movement Pregnancy Basic Helix-Loop-Helix Transcription Factors medicine Animals Molecular Biology Transcription factor Cells Cultured Mice Inbred ICR Gene knockdown Microarray analysis techniques Gene Expression Regulation Developmental Cell Differentiation Neural stem cell Mitochondria Cell biology DNA-Binding Proteins 030104 developmental biology medicine.anatomical_structure Gene Knockdown Techniques NEUROD1 Immunology Female Reactive Oxygen Species Oxidation-Reduction Transcription Factors Developmental Biology |
| Zdroj: | Development. |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.136382 |
| Popis: | 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 mitochondrial reactive oxygen species (mtROS) levels, 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 PGC-1α 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. |
| Databáze: | OpenAIRE |
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