Project/Area Number |
19F19387
|
Research Category |
Grant-in-Aid for JSPS Fellows
|
Allocation Type | Single-year Grants |
Section | 外国 |
Review Section |
Basic Section 44020:Developmental biology-related
|
Research Institution | Institute 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)
|
Co-Investigator(Kenkyū-buntansha) |
TANN JASON 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, 外国人特別研究員
|
Project Period (FY) |
2019-11-08 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2021: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2020: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2019: ¥300,000 (Direct Cost: ¥300,000)
|
Keywords | microtubule / dendrite / centrosomin / differentiation / nucleation / neuron differentiation / neuron |
Outline of Research at the Start |
The goal of this study is to gain a better understanding of the molecular mechanisms in neurite maintenance and development in neurons; this knowledge is crucial in developing strategies for neuronal repair in patients.
|
Outline of Annual Research Achievements |
Our previous studies emphasize a critical role for local amplification of microtubule generation pathways in differentiating neurons. Microtubule generation is also amplified in response to synaptic activity, and to neuron injury, where it plays a role in neuroprotection and regeneration. This raises the question of what molecular mechanisms underlie this amplification. In this project we looked for a new non-canonical process of microtubule generation in neurons; I have screened through unstudied proteins important for arbor development that act by driving postmitotic microtubule nucleation. Live imaging of microtubule nucleation activity (in vivo EB1 imaging), identifying a new factor required for this process. By manipulation of this factor I show that Drosophila c4da sensory neurons exhibit a dramatic reduction in microtubule nucleation at dendrite tips, with a significant modification in anterograde microtubule numbers. This reduction in microtubule nucleation is apparent across the entire microtubule arbor but is preferentially reduced at the dendrite tips. Live imaging of c4da neuron growth reveal that c4da neurons exhibit reduced arbor extension rate, and reduced branching frequency, leading to a stunted dendritic arbor. I have further investigated the activity of this protein in vitro, finding that it upregulates microtubule nucleation activity.
|
Research Progress Status |
令和3年度が最終年度であるため、記入しない。
|
Strategy for Future Research Activity |
令和3年度が最終年度であるため、記入しない。
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