Studies on developmental stage-dependent responsiveness of cerebral cortical neurons to netrin-1

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K06839
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Saitama Medical University
• Principal Investigator: Matsumoto Hideko 埼玉医科大学, 医学部, 助教 (00312257)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: 神経回路形成 / 大脳皮質ニューロン / 軸索ガイダンス / 軸索側枝形成 / ネトリン-1

Outline of Final Research Achievements

Netrin-1, an axon guidance cue, is known to exert various functions in the correct wiring of the nervous system during development. Our previous study raised the possibility of a shift in netrin-1 function from axon outgrowth to axon collateral branching in neurons dissociated from cerebral cortices of embryonic mice, and thus suggested developmental stage-dependent responsiveness of the neurons to netrin-1. In this research project we aimed to elucidate the mechanism underlying this developmental stage dependency of responsiveness to netrin-1 in cortical neurons.
The culture employed in our study was supposed to be highly heterogeneous containing multiple subpopulations of cortical neurons. We here focused on the subpopulations with collateral branches known in vivo, to analyze netrin-1-induced axon outgrowth/collateral branching. Axon collateral branching in E16 layer 2/3 callosal projection neurons, but not in corticospinal motor neurons, was promoted by netrin-1.

Free Research Field

発生神経生物学

Academic Significance and Societal Importance of the Research Achievements

大脳皮質ニューロンを総体として捉えた場合、マウス胎生14日(E14)ニューロンは軸索伸長反応、E16ニューロンは軸索側枝形成反応をネトリン-1に対して示すことがわかっていた。しかしながら大脳皮質ニューロンに種々の細胞集団が含まれることを考慮すると、特定の細胞集団が発生過程でその性質を変化させた可能性と、これら二種類の反応を示す細胞集団がそれぞれ別に存在する可能性がともに残されていた。本研究課題では大脳皮質ニューロンの各サブポピュレーションのうちⅡ/Ⅲ層脳梁交連ニューロンが、E16大脳皮質ニューロン総体で観察されていたネトリン-1依存的な軸索側枝形成を担う細胞集団の一つであることが示唆された。