Unravelling Mechanisms Underlying Termination of Neuronal Migration

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K07010
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: National Institute of Genetics
• Principal Investigator: Zhu Yan 国立遺伝学研究所, 遺伝形質研究系, 助教 (50464235)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: neuronal migration / termination / RNA-seq / bHLH / contactin-2 / chain migration / protein processing / Robo3

Outline of Final Research Achievements

One of the challenges to generate a functional brain is to correctly position different types of neurons into their proper final destinations. This process takes place at the termination phase of neuronal migration, but its underlying mechanisms are still poorly understood. This research aims to uncover these mechanisms using the mouse hindbrain as a model system. We have taken two different approaches, an unbiased transcriptome profiling approach using the recently developed genomic technology RNA-seq, and a candidate gene approach focusing on molecules that are regulated at post-transcriptional level. From these approaches, we have successfully identified a pair of transcription factors that are involved in migration and termination of migration, a receptor/ligand system that fine-tune the final location of neurons, and a post-translational regulation of a cell adhesion molecule by proteolysis during transition from migration to termination.

Free Research Field

神経発生

Academic Significance and Societal Importance of the Research Achievements

本研究の網羅的RNA-seqで得られた情報は、本研究の深化のみならず、将来的に様々な発見につながる波及効果をもたらすと期待される。神経細胞の位置異常は、神経発達障害における主要な原因である。実際、本研究で解析したいくつかの分子については、神経発達障害との関連が示唆されている。したがって、本研究はこれらの病気や病態の理解にも貢献すると考えられる。さらに、神経細胞移動の方向づけや、目的地で移動を停止する機構を理解することは、将来的に神経発達障害や神経障害の治療法を考える上でも有益な知見となるはずである。