Characterization of subtypes of precursor cells in the developing central nervous system

The role of radial glial cells as guides for migrating neurons is
well established, whereas their role as precursor cells is less
understood. Here we examined the composition of radial glial cells
and their proliferation in the mouse telencephalon during
development. We found that almost all radial glial cells
proliferate throughout neurogenesis. They consist of distinct
subsets identified by the differential co?localization of the
antigens RC2, the astrocyte-specific glutamate transporter (GLAST)
and the brain lipid-binding protein (BLBP). In addition, from on
late neurogenesis GLAST- and BLBP-antisera label precursor cells
with non-radial, but stellate morphology and thereby cover almost
the entire progenitor pool in the developing cerebral cortex. The
subsets identified by differential expression of these antigens
differ in their transcription factor expression and cell cycle
characteristics. Moreover, we could show by morphologically tracing
ventricular zone precursor cells, that cells with a radial
morphology constitute the majority of precursor cells in the CNS
during neurogenesis. Furthermore, we here present indications
showing that radial glial cells divide without retracting their
processes during M-phase, suggesting that radial glial cells can
proliferate and guide migrating neurons at a time. The molecular
signals regulating this crucial morphology of radial glial cells,
however, are largely unknown. Here we show that radial morphology
is impaired in the Reelin-deficient cerebral cortex of the reeler
mouse correlated to a decrease in the content of BLBP in radial
glial cells. These defects were restricted to the cerebral cortex,
but did not occur in the basal ganglia that exhibit normal
migration and radial glial cell differentiation in the reeler
mouse. These defects could be rescued in vitro by addition of
Reelin. Even in cultures of radial glial cells isolated by
fluorescent-activated cell sorting Reelin lead to an increase in
BLBP. These data therefore demonstrate a direct signalling of
Reelin to radial glial cells, thereby regulating their bipolar
morphology - most likely involving BLBP - in a region-specific
manner.