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Hartfuss, Eva (2003): Characterization of subtypes of precursor cells in the developing central nervous system. Dissertation, LMU München: Faculty of Biology
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Abstract

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.