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.
|Li, Yiwen; Rao, Prakash K; Wen, Rong et al. (2004) Notch and Schwann cell transformation. Oncogene 23:1146-52|
|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|
|Li, Y; Tennekoon, G I; Birnbaum, M et al. (2001) Neuregulin signaling through a PI3K/Akt/Bad pathway in Schwann cell survival. Mol Cell Neurosci 17:761-7|
|Porter, B E; Tennekoon, G (2000) Myelin and disorders that affect the formation and maintenance of this sheath. Ment Retard Dev Disabil Res Rev 6:47-58|
|Rutkowski, J L; Tuite, G F; Lincoln, P M et al. (1999) Signals for proinflammatory cytokine secretion by human Schwann cells. J Neuroimmunol 101:47-60|
|Thatikunta, P; Qin, W; Christy, B A et al. (1999) Reciprocal Id expression and myelin gene regulation in Schwann cells. Mol Cell Neurosci 14:519-28|
|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|
|Bharucha, V A; Peden, K W; Tennekoon, G I (1994) SV40 large T antigen with c-Jun down-regulates myelin P0 gene expression: a mechanism for papovaviral T antigen-mediated demyelination. Neuron 12:627-37|
|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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