Molecular mechanisms underlying acquisition and maintenance of cerebral cortical progenitor identity by Dmrt factors

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K06727
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Kyushu University (2018); Institute of Physical and Chemical Research (2015-2017)
• Principal Investigator: Konno Daijiro 九州大学, 生体防御医学研究所, 准教授 (00362715)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 神経前駆細胞 / 大脳皮質

Outline of Final Research Achievements

The spatio-temporal identity of neural progenitors and the regional control of neurogenesis are essential for the development of cerebral cortical architecture. This research project revealed a novel transcriptional network in which mammalian DM-domain containing transcription factors (Dmrts) confer the identity of the cerebral cortical progenitors by providing the positional information via dose-dependent suppression of developmental patterning factors including Gsx2 and pax6. Our results indicate that differential suppression of Gsx2 and Pax6 expression by Dmrt factors is a key mechanism not only for acquiring the cerebral cortical identity of progenitors but also for regulation of brain region size by negatively regulating neurogenesis. Thus, our findings provide new insights into the long-standing question of how vertebrate species acquired the cerebral cortex and how it enlarged in mammals during evolution.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

個体発生において多分化能を持つ胚性幹細胞からより運命の限定された体性幹細胞・前駆細胞に分化する過程の分子的理解は、発生現象を制御する分子機構の解明だけでなく、体性幹細胞を用いた再生医療の実現においても重要な意味を持つ。本研究では、胎生期大脳皮質神経前駆細胞の個性獲得・維持に必須の分子メカニズムを明らかにし、神経幹細胞・前駆細胞を用いた再生医療の実現に向けて新たな知見を提供する画期的な成果となった。