DETERMINANTS OF PROGENITOR CELL FATE IN THE CNS

Project Details

Description

Previous studies on the rodent forebrain have defined a single precursor
cell whose progeny can differentiate into two glial classes previously
thought to arise from separate progenitors. Preliminary studies suggest
that this precursor also has the potential to produce neurons as well as
both glial lineages. The goal of this grant will be to determine the
relative contributions of cell lineage and local environmental cues in
shaping the fate of this cell's progeny. To establish the role of lineage
in regulating fate, the following two hypotheses shall be tested: 1) that
this precursor is genetically determined to divide asymmetrically to
generate astroblasts and O-2A progenitors; and 2) that programmed cell
death regulates the timing of postnatal gliogenesis by eliminating cells
that develop inappropriately. To determine the role of cell-cell
interactions in regulating cell fate, co-culture experiments will be
performed with astrocytes, oligodendrocytes, neurons, and endothelial
cells to test the hypothesis that contact with, or secreted growth factors
from, these cells affect the differentiation of the multipotential
precursor. To determine whether the same precursor that produces both
classes of glia can also produce neurons, the multipotential glial
precursor will be purified using immunoselection and grown in culture
medium that fosters neuronal growth. A clonal analysis will establish
whether this progenitor is pluripotent. Finally, the purified progenitor
cell will be transplanted into fetal or juvenile hosts as another assay of
its developmental potential. The outcome of these studies will profoundly
influence current views on the development of the mammalian cerebral
cortex. These studies will provide insights into the cellular origins of
glial brain tumors and future characterizations of this precursor may
provide insights that will assist the medical profession in treating
individuals who suffer from neurological diseases and traumatic injuries
to the nervous system.
StatusFinished
Effective start/end date8/1/947/31/00

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $115,481.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $91,636.00
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Neuroscience(all)

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