Our long-term goals are: a) to obtain a comprehensive view of the regulation of the oligodendroglial lineage by protein growth factors and cell-cell contact; and b) to learn how to enhance oligodendroglial regeneration following multiple sclerosis and other demyelinating diseases. Studies relevant to these goals during the present granting period have shown: a) that germinal matrix oligodendroglial progenitor cells present in neonatal rat forebrain can fully regenerate the oligodendroglial lineage in cultures immunologically stripped of oligodendroglia and """"""""O-2A"""""""" oligodendroglial precursors if provided with platelet-derived growth factor (PDGF); b) that mature oligodendroglia can be induced to proliferate by treatment with a brain membrane-associated protein (""""""""brain membrane-associated oligodendroglial growth factor"""""""", BMOGF) that is distinct from other known oligodendroglial growth factors; and c) that mature oligodendroglia can be induced to """"""""dedifferentiate"""""""" to 0-2A cells when treated with basic fibroblast growth factor (basic FGF).
The specific aims of this competitive renewal are to: 1) clone and sequence BMOGF, determine its distribution and developmental expression, and investigate the mechanism by which it inhibits expression by oligodendroglia of myelin proteins; 2) determine the trophic effects of basic fibroblast growth factor (basic FGF) and platelet-derived growth factor (PDGF) on germinal matrix oligodendroglial progenitor cells; 3) determine the developmental pattern of expression by the oligodendroglial lineage of genes encoding receptors for basic FGF, PDGF, and other members of the protein tyrosine kinase family of plasma membrane growth factor receptors; and 4) examine in more detail the effects of basic FGF and BMOGF on mature oligodendroglia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025044-11
Application #
2445751
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Kerza-Kwiatecki, a P
Project Start
1987-09-01
Project End
1999-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
11
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Burns, Travis; Miers, Laird; Xu, Jie et al. (2014) Neuronopathy in the motor neocortex in a chronic model of multiple sclerosis. J Neuropathol Exp Neurol 73:335-44
Itoh, Takayuki; Horiuchi, Makoto; Ikeda Jr, Raymond H et al. (2014) ZPK/DLK and MKK4 form the critical gateway to axotomy-induced motoneuron death in neonates. J Neurosci 34:10729-42
Mills Ko, Emily; Ma, Joyce H; Guo, Fuzheng et al. (2014) Deletion of astroglial CXCL10 delays clinical onset but does not affect progressive axon loss in a murine autoimmune multiple sclerosis model. J Neuroinflammation 11:105
Moreno, Monica; Bannerman, Peter; Ma, Joyce et al. (2014) Conditional ablation of astroglial CCL2 suppresses CNS accumulation of M1 macrophages and preserves axons in mice with MOG peptide EAE. J Neurosci 34:8175-85
Jiang, Peng; Chen, Chen; Wang, Ruimin et al. (2013) hESC-derived Olig2+ progenitors generate a subtype of astroglia with protective effects against ischaemic brain injury. Nat Commun 4:2196
Daugherty, Daniel J; Selvaraj, Vimal; Chechneva, Olga V et al. (2013) A TSPO ligand is protective in a mouse model of multiple sclerosis. EMBO Mol Med 5:891-903
Chung, S-H; Guo, F; Jiang, P et al. (2013) Olig2/Plp-positive progenitor cells give rise to Bergmann glia in the cerebellum. Cell Death Dis 4:e546
Lang, Jordan; Maeda, Yoshiko; Bannerman, Peter et al. (2013) Adenomatous polyposis coli regulates oligodendroglial development. J Neurosci 33:3113-30
Moreno, Monica; Guo, Fuzheng; Mills Ko, Emily et al. (2013) Origins and significance of astrogliosis in the multiple sclerosis model, MOG peptide EAE. J Neurol Sci 333:55-9
Horiuchi, Makoto; Wakayama, Kouji; Itoh, Aki et al. (2012) Interferon regulatory factor 8/interferon consensus sequence binding protein is a critical transcription factor for the physiological phenotype of microglia. J Neuroinflammation 9:227

Showing the most recent 10 out of 123 publications