REGULATION OF POSTNATAL CORTICAL MULTIPOTENT PROGENITORS

Project: Research project

Project Details

Description

We have isolated multipotent progenitor cells from the cerebral cortex
independent of periventricular generative zones during the peak period
of early postnatal gliogenesis. These progenitor species undergo
cellular expansion and self-renewal in vitro in response to epidermal
growth factor and can generate neurons and glia, including myelin
protein-expressing oligodendrocytes. Glial progenitors derived from
these multipotent progenitors express the neurotrophin-3 receptor, trkC,
and application of neurotrophin-3 selectively promotes the expansion of
oligodendrocyte progenitors that require additional environmental
signals (ciliary neurotrophic factor, CNTF) for oligodendrocyte
differentiation. Neurotrophin-3 can also induce the expression of the
CNTFalpha receptor on glial progenitors derived from cortical
multipotent cells, while bone morphogenetic proteins promote the
generation of astrocytes and induce the expression of trkC on these
progenitor species. In preliminary in vivo studies, we have also shown
that transplanted cortical multipotent cells can undergo cellular
expansion and give rise to glial and neuronal progeny. In addition,
glial progenitors isolated from these multipotent cells proliferate in
vivo and give rise to oligodendrocytes and astrocytes. Cortical injury
enhances progenitor cell expansion and differentiation. In vitro
analysis: 1. To define the cellular properties of epidermal growth
factor-responsive cortical multipotent progenitors and their progeny:
A. Do these progenitors undergo long-term self-renewal? B. What is
the composition of neural lineage species derived from these multipotent
cells? C. What are the cellular actions of neurotrophin-3 on
oligodendroglial and astroglial development from glial progenitors
derived from these multipotent cells? In vivo analysis: 2. To define
the presence of appropriate early postnatal microenvironmental signals
for cortical progenitor cell development: A. Are the cellular profiles
of progenitor expansion, lineage restriction and differentiation
equivalent in vitro and in vivo? B. Are glial-restricted progeny
bipotent in vivo? C. Do different areas of the CNS neuraxis promote
distinct progenitor cell response profiles?

These studies will further our understanding of early progenitor cell
regulatory events in neural lineage development during normal mammalian
cerebral cortical maturation, identify pathologic mechanisms underlying
a range of genetic and acquired neurologic disorders, and promote the
development of novel regenerative strategies.
StatusFinished
Effective start/end date4/1/003/31/01

Funding

  • National Institute of Neurological Disorders and Stroke: $288,532.00

ASJC

  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience
  • Biomaterials
  • Developmental Biology
  • Immunology

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