Project Details

Description

The diverse functions of the vertebrate brain are made possible by its
enormous complexity at the cellular level. It is imperative, therefore,
that dynamic adhesions between neurons and glia that are involved in the
development of these complex cellular patterns be understood at the
molecular level. Cell surface molecules that mediate such cell-cell
adhesions have recently been identified but their functions are still
poorly understood. The long-term objective of this work is to understand
the role of molecules that mediate adhesion between neurons and glia both
in normal and aberrant brain development and function. A molecule (Ng-CAM) that is involved in neuron-glia cell adhesion has been
identified on neurons. This glycoprotein has been purified and antibodies
have been prepared that specifically recognize Ng-CAM and inhibit binding
between neurons and glial cells. Ng-CAM, however, does not appear on glia,
suggesting that another cell adhesion molecule that binds to Ng-CAM will be
found on these cells. The specific aims of this proposal are to evaluate
the function of Ng-CAM in development, to identify the ligand for Ng-CAM on
glia (Gn-CAM) and to understand in detail the mechanism of neuron-glia
binding. Specific antibodies to Ng-CAM will be used to determine the
distribution of Ng-CAM in vivo and to perturb critical developmental events
that are dependent on neuron-glia interactions, such as neuron migration on
glial fibers and the layering of cells in the retina. Gn-CAM will be
isolated by selecting molecules that neutralize inhibition by anti-(glial
cell) antibodies of neuron-glia cell adhesion, a modified form of the assay
used to purify Ng-CAM. Alternatively, Gn-CAM will be isolated on the basis
of its ability to bind to Ng-CAM. Specific antibodies to Gn-CAM will be
prepared and used to determine its localization in tissues and to evaluate
its role in neuron-glia adhesion by perturbation experiments. These studies will provide a better understanding of the role of
neuron-glia cell adhesion molecules in normal brain function. Because the
ratio of glial cells to neurons is higher in man than in any other species,
they may also help to provide key insights into the molecular bases of
specific neurological disorders, such as multiple sclerosis, muscular
dystrophy, gliomas and Alzheimer's Syndrome.Description
StatusFinished
Effective start/end date12/1/843/31/98

Funding

  • National Institutes of Health: $151,128.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $149,507.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $196,962.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $53,652.00

ASJC

  • Medicine(all)
  • Neuroscience(all)

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