| Project/Area Number |
23K21316
|
|---|
| Project/Area Number (Other) |
21H02496 (2021-2023)
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Multi-year Fund (2024)
Single-year Grants (2021-2023) |
|---|
| Section | 一般 |
|---|
| 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)
|
|---|
| Project Period (FY) |
2021-04-01 – 2025-03-31
|
| Project Status |
Granted (Fiscal Year 2024)
|
| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2024: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
|
|---|
| Keywords | Dendrite / Microtubule nucleation / microtubule / neurons / differentiation / regeneration / neuron / dendrite / axon / neurom / software / differentitaion / neuron differentiation / neuron regeneration |
|---|
| Outline of Research at the Start |
We expect that Pfn4 is present at the local center where microtubules are generated during dendrite arbor differentiation. It amplifies microtubule generation at these sites. We plan to investigate the localization of Pfn4 in the developing dendrite arbor. We will use in vivo imaging and develop new machine learning-based computer vision techniques to link the appearance of final arbor wiring features to the output of earlier local cytoskeletal organization events.
|
| Outline of Annual Research Achievements |
We are defining the cellular and molecular nature of microtubule generation mechanisms in neurons. Then, we will examine the functional significance of these mechanisms in arbor differentiation, connectivity, and plasticity. Disrupted microtubule regulation occurs in many neurological diseases, and new microtubule growth promotes neuron regeneration. Discovering specialized neuronal mechanisms for microtubule generation is one approach to providing unique drug targets for manipulating neuron differentiation and regeneration.
|
| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
We have examined Sonorin localization in the developing dendrite arbor. We examined the function of Sonorin in local control of microtubule generation using the same approaches as our previous studies. We have developed in vivo imaging with machine learning-based computer vision techniques to link the appearance of final arbor wiring features to the output of earlier local cytoskeletal organization events. We use synthetic images that mimic our imaging parameters to replace limited traditional manually annotated training datasets. This new approach dramatically advances our ability to segment our imaging data automatically. These new tools will make long-term, multi-measurement quantitative sequencing of live arbor differentiation a new standard for the field.
|
| Strategy for Future Research Activity |
We will use in vivo time-lapse tracking and EB1::GFP comet tracks, which bind the continuously expanding and retracting MT plus ends. Furthermore, MT nucleation plays a pivotal role in modulating post-injury neuron protection and regeneration. After neuron injury, MT nucleation activity significantly increases to promote the production of dynamic MTs throughout the neuron, this increase in dynamic MTs assists the injured neuron against injury-induced degradation and promotes neuron regeneration. Does Sonorin-mediated MT generation play a part in this process? I will investigate the function of Sonorin in a cellular context by inducing neuron damage to trigger a rapid upregulation of MT generation in the post-mitotic neurons and examine its role in injury-induced degeneration protection.
|
