2018 Fiscal Year Research-status Report
Unravelling Mechanisms Underlying Termination of Neuronal Migration
| Project/Area Number |
16K07010
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| Research Institution | National Institute of Genetics |
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Principal Investigator |
ZHU YAN 国立遺伝学研究所, 遺伝形質研究系, 助教 (50464235)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | neuronal migration / termination of migration / RNA-seq / Tag-1 / Bace1 |
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| Outline of Annual Research Achievements |
To understand how termination of neuronal migration is controlled, we performed: (1) RNA-seq based transcriptome profiling, and (2) examining the function and down-regulation of Tag-1. During this fiscal year, we performed gain- and loss-of-functional screening of candidate genes selected from RNA-seq, which uncovered several molecules in the process of termination. For approach (2), we discovered that Tag-1 can be processed by a beta-secretase 1 (Bace1). We showed that in vivo, Bace1 appears to regulate the Tag-1 protein level. A Bace1 resistant Tag-1 mutant prevents neurons from entering their termination sites.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
(1) Our RNA-seq experiment has generated rich molecular information, from which we have identified the involvement of a few molecules in termination of neuronal migration via functional screenings. Although there are further details to be worked out for these molecules, I believe we have reached the goal initially set by this grant.
(2) In the second candidate molecule approach, we have focused on Tag-1. We have demonstrated that Tag-1 plays an important role in maintaining chain migration of neurons and in preventing neurons from leaving their migratory stream prematurely. We further uncovered a role of a beta-secretase, Bace1, in processing Tag-1, which may contribute to its down-regulation prior to termination of migration.
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| Strategy for Future Research Activity |
Termination of neuronal migration is a multi-step process involving detachment from migratory stream, change of migratory polarity, and cessation of motility. Both our RNA-seq and Tag-1 projects have given us a molecular glimpse into these steps. However, the trigger that initiate the termination of migration is still unknown. A future line of research would be to probe into the nature of this trigger, in respect of which I would like to address several fundamental questions: (1) is the timing of migration termination merely controlled by extrinsic cues or to some extent an internal clock; (2) how is the termination of migration coupled with initiation of neuronal maturation. The datasets from our RNA-seq experiment may hold the clues and provide the tools to address these questions.
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| Causes of Carryover |
We have obtained a large amount of molecular information in this project. Although we have so far identified several molecules, we are still working on molecular details of their mechanisms in order to submit our study for publication. The incurring amount will be used to cover the costs of these experiments as well as paying for technical support.
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