Unexpectedly wide-range cell-cell contact via Delta-presenting lamellipodia-like protrusions in the mouse neuroepithelium

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K14837
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46020:Anatomy and histopathology of nervous system-related
• Research Institution: Kyoto University (2021-2022); Nagoya University (2018-2019)
• Principal Investigator: Kawaue Takumi 京都大学, 高等研究院, 特定助教 (50793858)
• Project Period (FY): 2021-03-01 – 2023-03-31
• Keywords: 発生・分化 / 細胞間相互作用 / 神経前駆細胞 / Delta-Notchシグナル伝達

Outline of Final Research Achievements

During mammalian brain development, cell contact-mediated interactions, such as Delta-Notch signaling, are important for the cell fate choice of the newborn cells. Although the fundamental molecular mechanism of Delta-Notch signaling is well known, how Delta-presenting cells contact with the neighbors to induce their Notch activation in developing 3D tissues has been challenging to address. In this study, we demonstrated that membrane-bound Delta molecules were enriched in lamellipodia-like protrusions that were extended from the apical process of differentiating cells. In addition, the decrease in lamellipodia-like structures increased the number of differentiating cells in the cerebral cortex. These results suggest that cell-cell contacts through microstructures are involved in cell fate choice for newborn cells.

Free Research Field

神経発生

Academic Significance and Societal Importance of the Research Achievements

本研究によって、哺乳類の大脳が形成される過程における細胞の運命選択の仕組みについて理解が深まった。また、細胞が持つ微細構造とそのダイナミクスが、細胞間のシグナル伝達の範囲を規定する重要な要素であることが明らかとなった。発展的展望として、シグナル伝達が活性化されるために必要な実質的な細胞間接触（接触面積・時間）について理解する必要があり、これから得られる知見は細胞の運命選択のみならず発生（正常・がん）・再生・疾患のメカニズム解明の糸口となる期待がある。