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The Journal of Neuroscience, November 15, 2001, 21(22):8863-8872
Specific Neurotrophic Factors Support the Survival of Cortical
Projection Neurons at Distinct Stages of Development
Lisa A.
Catapano,
Matthew W.
Arnold,
Francisco A.
Perez, and
Jeffrey D.
Macklis
Division of Neuroscience, Children's Hospital, and Department of
Neurology and Program in Neuroscience, Harvard Medical School, Boston,
Massachusetts 02115
Repair of specific neuronal circuitry in the neocortex may be
possible via neural precursor transplantation or manipulation of
endogenous precursors in situ. These approaches will
almost certainly require a detailed understanding of the mechanisms
that control survival and differentiation of specific neuronal
lineages. Such analysis has been hampered by the overwhelming diversity of neuronal types intermixed in neocortex and the inability to isolate
individual lineages. To elucidate stage-specific controls over the
survival of individual lineages of cortical neurons, we purified
immature callosal projection neurons (CPN) at distinct stages of
development from embryonic and postnatal mouse cortex by retrograde
fluorescence labeling, followed by fluorescence-activated cell
sorting. Purified CPN survive well in culture, acquire
stage-specific projection neuron morphologies, and express appropriate
neurotransmitters and growth factor receptors. Purified CPN are
dependent on exogenous trophic support for survival in a stage-specific
manner. Survival of postnatal day 2 (P2) to P3 and P6-P7 CPN is
promoted by overlapping but distinct sets of neurotrophic factors,
whereas embryonic day 19 CPN show less specificity of dependence on
peptide factors. These studies demonstrate for the first time the
stage-specific control by peptide growth factors over the survival of a
specific cortical neuronal lineage. Such information may be critical
for the future goal of directed differentiation of transplanted or endogenous precursors toward cellular repair of complex cortical circuitry.
Key words:
cortex; neocortex; callosal projection neuron; fluorescence-activated cell sorting; FACS; survival; neuronal culture; growth factors; neurotrophins
Copyright © 2001 Society for Neuroscience 0270-6474/01/21228863-10$05.00/0
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