| 研究課題/領域番号 |
23K05969
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| 研究機関 | 国立遺伝学研究所 |
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研究代表者 |
ZHU YAN 国立遺伝学研究所, 遺伝形質研究系, 助教 (50464235)
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| 研究期間 (年度) |
2023-04-01 – 2026-03-31
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| キーワード | Nhlh1/2 / Lhx2/9 / Isl1 / forebrain / commissural / Robo3 |
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| 研究実績の概要 |
The objective of this research is to understand how Nhlh1/2 regulate commissural neuronal fate, and what other functions Nhlh1/2 may have in the differentiation of neurons. I have so far identified regionally-acting molecular mechanisms that intersect with the global Nhlh1/2 mechanism to regulate the axon laterality of commissural neurons. A part of this finding has been incorporated in our recent accepted paper. I have also performed RNA-seq experiments to identify comprehensively the downstream targets of Nhlh1/2. In addition, I have generated epitope-tagged knock-in mouse lines, namely FLAG-Nhlh1 and HA-Nhlh2 mice, which would aid the identification of co-factors and downstream targets.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
We were able to uncover regionally-acting modulatory mechanisms of Nhlh1/2 in regulating Robo3 expression by carefully studying literatures and making use of published single cell RNA-seq data from others. We also produced the epitope tag knock-in mouse lines smoothly by collaborating with the mouse unit in our institute.
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| 今後の研究の推進方策 |
In the second year of this 3 year project, I plan to put our main effort in identifying the role of Nhlh1/2 during the forebrain development. RNA-seq experiment comparing wild type, Nhlh1/2 double mutant or Nhlh1/2 overexpressed forebrain tissues should generate candidate downstream target molecules with which we can generate hypothesis on the function of Nhlh1/2 in this brain region. With the availability of the epitope knock-in mice lines, we can also examine in detail the cell types Nhlh1 and Nhlh2 are expressed in, as well as performing Chip-Seq experiment to pull out downstream target. The above two approaches should generate working model which we can test using the Nhlh1/2 double mutant mice.
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| 次年度使用額が生じた理由 |
For the second year of funding period, we will spend the budget completing the second RNA-seq experiment focusing on the forebrain region. We will also perform detailed expression analysis using the FLAG-Nhlh1 and HA-Nhlh2 knock-in mouse lines. In addition, we will perform Chip-Seq experiments to narrow down on direct downstream targets of Nhlh1/2. Based on the outcome of these three lines of research, we will then generate a working model on the functions of Nhlh1/2 and will test this model using the Nhlh1/2 double mutant mice we previously generated.
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