Plag1 regulates neuronal gene expression and neuronal differentiation of neocortical neural progenitor cells

• Published in: Genes to cells : devoted to molecular & cellular mechanisms 2019-10, Vol.24 (10), p.650-666
• Main Authors: Sakai, Hiroshi, Fujii, Yuki, Kuwayama, Naohiro, Kawaji, Keita, Gotoh, Yukiko, Kishi, Yusuke
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes; Cell differentiation; Cell Differentiation - physiology; Cell Proliferation - physiology; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Embryos; Gene Expression; Gene Expression Regulation; Glial cells; Glial stem cells; Hmga2; HMGA2 Protein - genetics; HMGA2 Protein - metabolism; Mice; Neocortex; Neocortex - cytology; Neocortex - metabolism; Neocortex - physiology; neural progenitor cells; Neural stem cells; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neural Stem Cells - physiology; Neurogenesis; neuronal differentiation; Neuronal-glial interactions; Neurons - cytology; Neurons - metabolism; Neurons - physiology; Plag1; Progenitor cells
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/gtc.12718

Neural progenitor cells (NPCs, also known as radial glial progenitors) produce neurons and then glial cells such as astrocytes during development of the mouse neocortex. Given that this sequential generation of neural cells is critical for proper brain formation, the neurogenic potential of NPCs must be precisely controlled. Here, we show that the transcription factor Plag1 plays an important role in the regulation of neurogenic potential in mouse neocortical NPCs. We found that Hmga2, a key neurogenic factor in neocortical NPCs, induces expression of the Plag1 gene. Analysis of the effects of over‐expression or knockdown of Plag1 indicated that Plag1 promotes the production of neurons at the expense of astrocyte production in embryonic neocortical cultures. Furthermore, over‐expression of Plag1 promoted and knockdown of Plag1 suppressed neuronal differentiation of neocortical NPCs in vivo. Transcriptomic analysis showed that Plag1 increases the expression of a set of neuronal genes in NPCs. Our results thus identify Plag1 as a regulator of neuronal gene expression and neuronal differentiation in NPCs of the developing mouse neocortex. Overexpression of the transcription factor Plag1 promoted neuronal differentiation of neural progenitors in the mouse neocortex.