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Oligodendrocyte biology and role in MS
We are interested in understanding the biology of oligodendrocytes
(OLGs), the cells that synthesize and maintain central nervous system myelin.
Current efforts are directed toward unraveling the events and identifying
the molecules that signal the beginning of a myelinogenic phenotype. For
this we employ an in vitro model system consisting of pure cultures
of OLGs isolated from young brains. We have found that these OLGs acquire
a myelinogenic phenotype upon adhesion to a polylysine (PL)-coated surface
in the presence of 20% horse serum, or on plates coated first with PL and
then with GRASP (a heparin-binding horse serum glycoprotein) in the absence
of added serum. Among the events that accompany adhesion figure the assembly
of an extracellular matrix. Heparan sulfate proteoglycans (HSPGs) are major
constituents of this matrix. We hypothesize that the binding of GRASP to
a surface receptor unleashes a cascade of reactions that culminate in OLG
differentiation. We further postulate that the amassing of an extracellular
matrix constitutes an initial and key step in this process. Ongoing research
projects aim at proving/disproving these hypotheses. Specifically, we are
trying to identify and characterize GRASP's receptor. We are also characterizing
- structurally and functionally - matrix components, both membrane-bound
and secreted. Additionally, we are attempting to identify adhesion-induced
genes
that might be instrumental in defining the myelinogenic phenotype.
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