| Project/Area Number |
23K05969
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 46010:Neuroscience-general-related
|
|---|
| Research Institution | National Institute of Genetics |
|---|
Principal Investigator |
ZHU YAN 国立遺伝学研究所, 遺伝形質研究系, 助教 (50464235)
|
|---|
| Project Period (FY) |
2023-04-01 – 2026-03-31
|
| Project Status |
Granted (Fiscal Year 2023)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2025: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2024: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2023: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | Nhlh1/2 / Lhx2/9 / Isl1 / forebrain / commissural / Robo3 / Nhlh1 and Nhlh2 / Neuronal identiy / regulatory network |
|---|
| Outline of Research at the Start |
In this research, I address the question of what gene regulatory programs specify neuronal attributes that are shared across divergent neuron classes via the lens of a pair of bHLH transcription factors, Nhlh1 and Nhlh2, recently identified by us as a global mechanism to assign axon laterality.
|
| Outline of Annual Research Achievements |
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.
|
| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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.
|
| Strategy for Future Research Activity |
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.
|
