Spatiotemporal heterogeneity of CNS radial glial cells and their transition to restricted precursors

Abstract

Radial glia are among the first cells that develop in the embryonic central nervous system. They are progenitors of glia and neurons but their relationship with restricted precursors that are also derived from neuroepithelia is unclear. To clarify this issue, we analyzed expression of cell type specific markers (BLBP for radial glia, 5A5/E-NCAM for neuronal precursors and A2B5 for glial precursors) on cortical radial glia in vivo and their progeny in vitro. Clones of cortical cells initially expressing only BLBP gave rise to cells that were A2B5+ and eventually lost BLBP expression in vitro. BLBP is expressed in the rat neuroepithelium as early as E12.5 when there is little or no staining for A2B5 and 5A5. In E13.5-15.5 forebrain, A2B5 is spatially restricted co-localizing with a subset of the BLBP+ radial glia. Analysis of cells isolated acutely from embryonic cortices confirmed that BLBP expression could appear without, or together with, A2B5 or 5A5. The numbers of BLBP+/5A5+ cells decreased during neurogenesis while the numbers of BLBP+/A2B5+ cells remained high through the beginning of gliogenesis. The combined results demonstrate that spatially restricted subpopulations of radial glia along the dorsal-ventral axis acquire different markers for neuronal or glial precursors during CNS development.

Neural Stem/Progenitor Cell Clones as Models for Neural Development and Transplantation

“…Because of their transient nature, isolation and propagation of RG in vitro have been unsuccessful. The v-myc immortalized RG clones (RG3.6 and L2.3) showed high proliferation rate in the presence of FGF2 and maintained RG markers over many passages, which provides an in vitro model system to allow examination and manipulation on this cell type (Hasegawa et al, 2005;Li et al, 2004). We did observe a gradual change in expression of certain markers in cultured RG clones during passage.…”

Phenotypic and functional characterization of adult brain neuropoiesis

“…Furthermore, we propose that a subpopulation of A2B5 ϩ cells that coexpresses nestin and low levels of GFAP could represent the founders for the SVZ-specific generation of interneurons. Even though the monoclonal antibody A2B5 is not cell-type-specific, because it detects different precursor cells in a variety of developing and adult CNS structures (30-34), we found it intriguing that this antigen is also expressed by a subpopulation of radial glial cells in the lateral ganglionic eminence (LGE) between embryonic days 13.5 and 15.5 (35). The LGE supplies interneurons to the olfactory bulb during brain development (36) and is an ancestor of the postnatal͞adult striatal SVZ.…”

Neurofibromin Regulates Neural Stem Cell Proliferation, Survival, and Astroglial Differentiation In Vitro and In Vivo

“…Expression of the Sox2 transcription factor is a molecular signature of proliferating stem/progenitor cells, and Sox2 expression is necessary for maintaining neural stem/progenitor cell identity (Uwanogho et al, 1995;Graham et al, 2003). Similarly, BLBP is expressed as early as E10 in multipotent proliferating cells within the CNS, which are thought to represent progenitors of astroglial cells (Feng et al, 1994;Li et al, 2004). Finally, both Olig1 and Nkx2.2 are expressed in cells within the developing neural tube (Lu et al, 2000;Zhou et al, 2001;Liu et al, 2004).…”