Involvement of Dmrt gene family in the embryonic development of the mammalian neocortex

• Project/Area Number: 24500395
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: KONNO Daijiro 独立行政法人理化学研究所, 多細胞システム形成研究センター, 研究員 (00362715)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 神経幹細胞 / 国際情報交換

Outline of Final Research Achievements

In this research project, we report that Dmrt3 and Dmrta2, two related mammalian DM domain-containing transcription factors (Dmrt), are critically involved in maintaining the neocortical identity of neural progenitor cells in the developing mouse brain. These factors are highly expressed in neural progenitor cells in the dorsal telencephalon at early stages of cortical development. Dmrt3 and Dmrta2 double mutant brains exhibited a conversion of neural progenitor characteristics in the dorsal telencephalon from a neocortical (glutamatergic neuron-generating) to a subcortical (GABAergic neuron-generating) identity, suggesting that Dmrt3/Dmrta2 negatively regulate the genetic pathway, establishing the ventral cell fate in the telencephalon. Our results suggest a novel mechanism for maintaining neural progenitor characteristics, in which Dmrt3/Dmrta2 blocks ventralization of neural progenitors, thereby ensuring the proper development of neocortical neural progenitors.

Research Products

• [Journal Article] Incorporation of histone H3.1 suppresses the lineage potential of skeletal muscle (2015)
  • Author(s): Harada A, Maehara K, Sato Y, Konno D, Tachibana T, Kimura H, Ohkawa Y.
  • Journal Title: Nucleic Acids Research Volume: 43 Issue: 2 Pages: 775-786
  • DOI: 10.1093/nar/gku1346
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Improving spinning disk confocal microscopy by preventing pinhole cross-talk for intravital imaging. (2013)
  • Author(s): Togo Shimozawa et al.
  • Journal Title: Proceeding of the National Academy of Sciences of the United States of America Volume: 110 Issue: 9 Pages: 3399-3404
  • DOI: 10.1073/pnas.1216696110
  • Peer Reviewed
• [Journal Article] The mammalian DM domain transcription factor Dmrta2 is required for early embryonic development of the cerebral cortex. (2013)
  • Author(s): Konno D, Iwashita M, Satoh Y, Momiyama A, Abe T, Kiyonari H, Matsuzaki F.
  • Journal Title: PLoS One Volume: 110(9) Issue: 10 Pages: 3399-404
  • DOI: 10.1371/journal.pone.0046577
  • Peer Reviewed
• [Journal Article] Chd2 interacts with H3.3 to determine myogenic cell fate. (2012)
  • Author(s): Harada A, Okada S, Konno D, Odawara J, Yoshimi T, Yoshimura S, Kumamaru H, Saiwai H, Tsubota T, Kurumizaka H, Akashi K, Tachibana T, Imbalzano AN, Ohkawa Y.
  • Journal Title: EMBO J Volume: 31(13) Pages: 2994-3007
  • Peer Reviewed
• [Presentation] Spatial and temporal regulation of neural stem cell identity in the mammalian cerebral cortex by Dmrt family transcription factors. (2015)
  • Author(s): Konno, D and Matsuzaki, F
  • Organizer: CDB Symposium 2015
  • Place of Presentation: RIKEN CDB, Kobe, Japan
  • Year and Date: 2015-03-23 – 2015-03-25