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Transcriptional controls link neuron growth rate, nutrition, and the developmental clock

Publicly Offered Research

Project AreaInterplay of developmental clock and extracellular environment in brain formation
Project/Area Number 19H04793
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Moore Adrian  国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (30442932)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
KeywordsNeuron growth / chromatin regulators / transcription programs / Dendrite / Transcription Factor / Microtubule / Chromatin / Neuron Differentiaiton / neuron / dendrite / differentiation / temporal program / myosin / microtubules / actin / diffrentiation / time
Outline of Research at the Start

To determine how developmental clock processes, regulate dendrite arbor patterning, recently we used in vivo live imaging of Drosophila c sensory neurons to follow the complete temporal sequence of arbor patterning events. Key to this is the timing of a switch in growth rates: early establishment of the main arbor field requires rapid outgrowth; this then transitions into a slow growing maturation phase. We predict that the developmental clock which times this transition consists of both a cell intrinsic counting component and anexternal regulatory component.

Outline of Annual Research Achievements

The nervous system expands massively in size from its formation during embryogenesis until maturity; insufficient brain growth is a significant cause of intellectual disability. As neurons don’t divide, this expansion is supported primarily through enormous cellular growth that scales proportionally with the growth of the organism. Here, we utilized Drosophila larval body wall sensory neurons as a model system to investigate this scaling program. We carried out genome-wide mapping of transcription start sites at single base pair-resolution during scaling. Through motif- and Chip seq- activity mapping, we identified the prevalent chromatin architectural proteins that drive these promoter cohorts to power cellular scaling. In parallel, through systematic genetic screening of the loci controlled by these promoter cohorts, coupled with multi-dimensional morphometric analysis, we identified key cell biological effectors of this program. We found that these effectors of scaling also introduce variance to dendritic parameters of individual neurons, allowing for diversification of arbor morphology;a trait argued to potentially contribute to the emergence of higher order nervous system activity. Some neuron types are bigger than others; for example, the large class IV da neurons grow quicker and to a larger mature arbor size than other body wall sensory neurons.

Research Progress Status

令和2年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和2年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (5 results)

All 2020 2019

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] Atypical Myosin Tunes Dendrite Arbor Subdivision2020

    • Author(s)
      Yoong LF, Lim HK, Tran H, Lackner S, Zheng Z, Hong P, Moore AW
    • Journal Title

      Neuron

      Volume: online Issue: 3 Pages: 452-467.e8

    • DOI

      10.1016/j.neuron.2020.02.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] The control and effector network of neuronal scaling and neuron-level dendritic arbor diversification2020

    • Author(s)
      Yun Jin Pai
    • Organizer
      43rd annual meeting of the molecular biology society of Japan
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Specification of neuron Type: From Transcription to Wiring2020

    • Author(s)
      Adrian Moore
    • Organizer
      5th Asia Pacific Drosophila Research Conference
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neuro-differentiation: From Transcription to Wiring2020

    • Author(s)
      Adrian Moore
    • Organizer
      Asia Pacific Drosophila Conference
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] The control and effector network of neuronal scaling and neuron-level dendritic arbor diversification2019

    • Author(s)
      Yun Jin Pai
    • Organizer
      Cold Spring Harbor Neurobiology of Drosophila
    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2021-12-27  

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