2000 Fiscal Year Final Research Report Summary
THE ANALYSIS OF PATHOGENESIS OF AMYOTROPHIC LATERAL SCLEROSIS BASED ON THE ESTABLISHMENT OF IN VITRO MOTOR NEURONAL CELL LINES
| Project/Area Number |
11670156
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
TANABE Yasuto Osaka Bioscience Institute, 4^<TH> DEPARTMENT, VICE HEAD, 第4研究部, 研究副部長 (10311309)
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| Co-Investigator(Kenkyū-buntansha) |
KAKITUKA Akira Osaka Bioscience Institute, 4<@D1TH@>D1 DEPARTMENT, HEAD, 第4研究部, 研究部長 (80204329)
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| Project Period (FY) |
1999 – 2000
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| Keywords | MOTOR NEURON / AMYOTOROPHICLATERAL SCLEROSIS / TRANSCRIPTION FACTORS / INDUCTION / P19 CELLS / SPINALOORD |
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| Research Abstract |
Previous works concerning the issues of neuronal diversification were able to show that the specification of neuronal identity within the CNS is controlled by the localized action of several environmental signals. These signaling molecules specify the identity of neighboring cells by inducing the expression of cell intrinsic signaling molecules, many of which are transcription factors. And these transcription factors, in turn, regulate expression of the downstream genes for the acquisition of the individual neuronal identities.
Sonic hedgehog (Shh) is known to be a signaling molecule that trigger the differentiation of motor neurons, but the intervening steps between the actions of Shh and the specification of motor neuron identity were poorly understood. I have employed a differential screen of a cDNA library derived from a single early-specified motor neuron, and have identified a novel homeobox gene, MNR2, expressed by motor neuron progenitor cells and transiently by postmitotic motor neurons. The ectopic expression of MNR2 in the developing spinal cord in vivo was shown to initiate a program of motor neuron differentiation. characterized by the expression of motor neuron transcription factors, by neurotransmitter phenotype, and by axonal trajectory. These results indicate that the Shh-mediated induction of a single transcription factor, MNR2, is sufficient to direct the motor neuron differentiation.
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