The experimental attempt for brain evolution by increase of neurons in mouse cerebral cortex

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K14569
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: OKADO haruo 公益財団法人東京都医学総合研究所, 脳発達・神経再生研究分野, プロジェクトリーダー (60221842)
• Co-Investigator(Kenkyū-buntansha): 平井 志伸 公益財団法人東京都医学総合研究所, 脳発達・神経再生研究分野, 研究員 (00625189)
• Co-Investigator(Renkei-kenkyūsha): TANAKA Kenji 慶應義塾大学, 生物学的精神医学, 特任准教授 (30329700)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: RP58 / 大脳皮質 / RP58 大脳新皮質 外側脳室下帯OSVZ

Outline of Final Research Achievements

RP58 KO mice display an increase in progenitor cells due to inhibition of cell cycle exit. RP58 KO cortex shows a three-layered structure with an outer Pax6 layer, which resembles the primate outer subventricular zone (OSVZ). The OSVZ is known to important for increase of cortical neurons in the primate brain. We propose that a primate-like cortex can be generated from a rodent cortex by modulating cell cycle exit of progenitor cells. For example, inhibition of RP58 activity early in development may increase progenitor cell number leading to the formation of an OSVZ. Subsequent activation of RP58 may increase differentiation of mature neurons leading to formation of a large cortex with gyruses.
To examine the hypothesis, we tried to rescue these cells by RP58 supply at good timing using in utero electropolation or adenovirus vectors. However, we found these methods are insufficient in efficiency. Now we start FAST system for regulation of RP58 transcription.

Free Research Field

神経生物学