Abstract
Radial glial cells (RGs) originally considered to provide scaffold to the radially migrating neurons constitute a heterogeneous population of the regionally variable precursor cells that generate both neurons as well as glia depending upon the location and the timing of development. Hence specific immunohistochemical markers are required to specify their spatiotemporal location and fate in the neurogenic and gliogenic zones. We hypothesize S100β as a potential and unified marker for both primary and secondary progenitors. To achieve this, cryocut sections from rat brains of varied embryonic and postnatal ages were immunolabeled with a combination of antibodies, i.e., S100β + Nestin, Nestin + GFAP and S100β + GFAP. A large population of the primary and secondary progenitors, lining the VZ and SVZ, simultaneously co-expressed S100β and nestin establishing their progenitor nature. A downregulation of both S100β and nestin noticed by the end of the 1st postnatal week marks their differentiation towards neuronal or glial lineage. In view of the absence of co-expression of GFAP (glial fibrillary acidic protein) either with S100β or nestin, the suitability of accepting GFAP as an early marker of RG’s was eliminated. Thus the dynamic expression of S100β in both the neural stem cells (NSCs) and RGs during embryonic and early neonatal life is associated with its proliferative potential and migration of undifferentiated neuroblasts and astrocytes. Once they lose their potential for proliferation, the S100β expression is repressed with its reemergence in mature astrocytes. This study provides the first clear evidence of S100β expression throughout the period of neurogenesis and early gliogenesis, suggesting its suitability as a radial progenitor cell marker.
Highlights
Radial glia are the primary progenitor cells during early embryonic neurogenesis with a capacity to generate all types of neurons and glia (Noctor et al, 2001, 2002; Tamamaki et al, 2001; Rowitch and Kriegstein, 2010)
S100β as a Radial Progenitor Cell Marker To visualize the radial glial progenitor cells in the developing rat brain during the embryonic and postnatal life, we used a monoclonal antibody against nestin, a well-established marker known to label both the neural stem cells (NSCs)/neuroepithelial cells and radial glial progenitor cells (Lendahl and McKay, 1990; Parnavelas and Nadarajah, 2001)
While S100β has been well reported to have a role in proliferation and differentiation and a marker of mature astrocytes, Haubensak et al (2004) reported it’s expression in primary radial glial scaffolds involved in Purkinje progenitor exit from the ventricular zone (VZ)
Summary
Radial glia are the primary progenitor cells during early embryonic neurogenesis with a capacity to generate all types of neurons and glia (Noctor et al, 2001, 2002; Tamamaki et al, 2001; Rowitch and Kriegstein, 2010). In addition to the VZ, the embryonic sub ventricular zone (SVZ) having cells derived from RG is considered as a major site for neurogenesis (Noctor et al, 2001, 2004, 2008; Tarabykin et al, 2001; Smart et al, 2002; Nieto et al, 2004; Zimmer et al, 2004; Pontious et al, 2008; Kriegstein and Alvarez-Buylla, 2009). Subsequent imaging studies on the divisions of precursor cells within the SVZ have demonstrated their neurogenic potential (Miyata et al, 2004; Noctor et al, 2004)
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