Analysis of the internal or mechanical cues to regulate planar polarity for the neural tube formation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07427
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Nishimura Tamako 奈良先端科学技術大学院大学, 先端科学技術研究科, 助教 (40415261)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: Celsr1 / neural tube / Wnt / I-BAR

Outline of Final Research Achievements

When the neuroepithelial layer is invaginated during the neural tube closure, a planar　polarity protein Celsr1 is distributed to the cell-cell contacts along the dorsoventral axis and contracts actin filaments in that direction. However, upstream signals that polarize Celsr1 are unknown.
Therefore, we investigated the possibility that mechanical stimuli added to cells or internal stimuli such as Wnt might be involved in the process. As a result, some of the Wnt molecules were secreted through microvesicles, which are extracellular vesicles derived from the plasma membrane, and activated the Wnt receptor. Furthermore, I-BAR proteins, which deform and cleave the plasma membrane, were found to be involved in the Wnt secretion.
We would like to elucidate next whether these phenomena are involved in the polar-polarized distribution of Celsr1.

Free Research Field

Cell biology, Developmental biology

Academic Significance and Societal Importance of the Research Achievements

内的刺激因子Wntは、これまでタンパク質複合体やエンドソーム系細胞外小胞エクソソームを介して分泌されると考えられており、細胞突起由来のマイクロベシクルを介して分泌されうることを示したのは我々が初めてである。I-BARタンパク質MIMは神経管形成への関与が報告されており、その作用がCelsr1の極性分布を介する可能性がある。神経管の異常形成は新生児の先天性疾患で2番目に多く、Celsr1の様々な変異が報告されている。Celsr1を介したシグナル伝達の解明により、異常の原因解明や予防・治療につながる可能性がある。