| Project/Area Number |
17300102
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neuroscience in general
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
SAITO Tetsuichiro Chiba University, Graduate School of Medicine, Professor (00202078)
|
|---|
| Project Period (FY) |
2005 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥15,400,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2007: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2006: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2005: ¥6,200,000 (Direct Cost: ¥6,200,000)
|
|---|
| Keywords | neuron / development & differentiation / neural network / spinal cord / mammal / transgenic mouse / transcription factor / homeobox gene / ホメオボックス遺伝 |
|---|
| Research Abstract |
We have analyzed molecular mechanisms underlying the formation and function of neural networks in the mouse spinal cord dorsal horn. Axon projection of commissural neurons in the spinal cord has been well studied. However, molecules and mechanisms to regulate their differentiation remained largely unknown. We have established a highly efficient gene transfer method based on in vivo elechroporation in the mouse central nervous system for functional analysis of genes. By gain- and loss-of-function analyses using this method, in combination with transgenic and knockout mice, we have revealed that the fate of commissural neurons is determined by the transcriptional cascade from a proneural gene, Math1, to a homeobox gene, Mbh1, and that Mbh1 is required for the differentiation of commissural neurons. Moreover, chromatin immunoprecipitation assays showed that the Math1 protein directly activates expression of Mbh1 through its enhancer. We have curried out microarray analyses to find downstream genes of the cascade using RNAs from the Mbh1-misexpressed spinal cord. Many genes were activated by misexpression of Mbh1. Some of them, such as Netrin and Slit receptors, Doc and Robes, have been known to play pivotal roles in the projection of axons. Their expressions were regulated in a spatiotemporally organized manner by the cascade from Math1 to Mbhl, suggesting that the cascade is essential for the projection of commiecnral axons.
|
