MOLECULAR ANALYSIS OF NEURAL CELL DEVELOPMENT

Project: Research project

Project Details

Description

The long term objectives of this project are to understand at the
molecular level some of the genetic and epigenetic factors
responsible for cell differentiation and interactions in the
mammalian Central Nervous System. With this knowledge it will
be possible to understand more fully a wide range of
developmental disorders and degenerative diseases that affect the
nervous system.

We have defined a cell surface carbohydrate determinant that
shows position-dependent expression in the developing retina,
transient expression in a number of cortical regions and a
developmentally regulated secondary modification in cerebellum.
We have identified the structure of this molecule in retina and
cortex and intend to test whether specific enzymes are rate-
limiting in its biosynthesis. A variety of in vitro culture systems
will be used to study the possible role of this molecule in
regulating cell interactions and process migration.

Available monoclonal antibodies, and others to be produced
against growth comes from embryonic rat cerebral cortex, will be
used to define molecules on these organelles. Molecules that are
on all growth cones, and those that are restricted to growth cones
of particular cell types, will be studies for their potential role in
selective fasciculation and directional process outgrowth.

One class of growth cone molecules that will be studied in detail
are those responsible for interactions that trigger biochemical
responses such as increases in synaptic vesicle membrane protein
expression, related to synapse formation.

The possible role of the membrane bound proto-oncogenes c-src
and c-yes in linking cell surface interactions to changes in gene
expression will be examined since they show striking correlative
changes in level and activity during neural development.

Finally, since many of the cell interactions being studied are
accompanied by, or cause, alterations in gene activity, this
proposal will study the similarities and differences in activation
mechanisms of a set of genes expressed in photoreceptors at
discrete times during retinal development.

Together, the specific aims in this proposal represent a focussed
effort to define and understand the function of molecules
expressed on neural cells and their processes during important
phases of growth and cell interaction.
StatusFinished
Effective start/end date12/31/892/28/99

Funding

  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke

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