The long-term goal of the work described is to understand how extracellular signals orchestrate changes in the Schwann cell phenotype. The main hypothesis to be tested is that the Ras/MAP kinase pathway acting through transcription factors AP-2 and C/EBP increases myelin P0 expression and the extracellular signal that triggers this pathway is laminin, a component of basal lamina.
The aims of this proposal are to investigate whether MAP kinase and cAMP activation of myelin genes occur through these two transcription factors and to demonstrate that laminin induction of myelin genes utilizes the ras pathway. An understanding of the mechanism whereby the Schwann cell phenotype is regulated can allow for experimental manipulation of this cell which might be helpful in several medical areas such as designing therapies for demyelinating diseases and transplantation for spinal cord regeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021700-14
Application #
2655441
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Kerza-Kwiatecki, a P
Project Start
1990-02-01
Project End
2001-01-31
Budget Start
1998-02-01
Budget End
1999-01-31
Support Year
14
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Li, Yiwen; Gonzalez, Marco I; Meinkoth, Judy L et al. (2003) Lysophosphatidic acid promotes survival and differentiation of rat Schwann cells. J Biol Chem 278:9585-91
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Magnani, P; Thomas, T P; Tennekoon, G et al. (1998) Regulation of glucose transport in cultured Schwann cells. J Peripher Nerv Syst 3:28-36
Nikam, S S; Tennekoon, G I; Christy, B A et al. (1995) The zinc finger transcription factor Zif268/Egr-1 is essential for Schwann cell expression of the p75 NGF receptor. Mol Cell Neurosci 6:337-48
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Gutmann, D H; Tennekoon, G I; Cole, J L et al. (1993) Modulation of the neurofibromatosis type 1 gene product, neurofibromin, during Schwann cell differentiation. J Neurosci Res 36:216-23

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