Astroglial cells in the external granular layer are precursors of cerebellar granule neurons in neonates

Abstract

It is well established that cerebellar granule cell precursors (GCPs) initially derive from progenitors in the rhombic lip of the embryonic cerebellar primordium. GCPs proliferate and migrate tangentially across the cerebellum to form the external granule cell layer (EGL) in late embryogenesis and early postnatal development. It is unclear whether GCPs are specified exclusively in the embryonic rhombic lip or whether their precursor persists in the neonate. Using transgenic mice expressing DsRed under the human glial fibrillary acidic protein (hGFAP) promoter, we found 2 populations of DsRed + cells in the EGL in the first postnatal week defined by bright and faint DsRed fluorescent signal. Bright DsRed + cells have a protein expression profile and electrophysiological characteristics typical of astrocytes, but faint DsRed + cells in the EGL and internal granule cell layer (IGL) express markers and physiological properties of immature neurons. To determine if these astroglial cells gave rise to GCPs, we genetically tagged them with EGFP or βgal reporter genes at postnatal day (P)3-P5 using a hGFAP promoter driven inducible Cre recombinase. We found that GFAP promoter + cells in the EGL are proliferative and express glial and neural stem cell markers. In addition, immature granule cells (GCs) en route to the IGL at P12 as well as GCs in the mature cerebellum, 30 days after recombination, express the reporter protein, suggesting that GFAP promoter + cells in the EGL generate a subset of granule cells. The identification of glial cells which function as neuronal progenitor cells profoundly impacts our understanding of cellular plasticity in the developing cerebellum.

Loss of adenomatous polyposis coli in Bergmann glia disrupts their unique architecture and leads to cell nonautonomous neurodegeneration of cerebellar Purkinje neurons

“…In addition, a small portion (7.2%, n=3 mice) of NeuN-positive granule cells expressed GFP (Fig. 2D), which is consistent with the recent report that some progenitors that give rise to postnatally born granule cells can express GFAP (Lee et al 2005; Schuller et al 2008; Silbereis et al 2010). Parvalbumin-positive basket/stellate cells did not express GFP (Fig.…”

Characterization of Apoptosis Signaling Cascades During the Differentiation Process of Human Neural ReNcell VM Progenitor Cells In Vitro

“…We observed that few proliferating ReNcell VM cells were GFAP-positive, which appears to be a sign for spontaneous astroglial differentiation, as suggested by Donato et al (2007). But while GFAP is known as the main astroglial marker during astrogliogenesis, we need to keep in mind that it is also expressed in other cell types, including neural stem cells and older neurons (Hol et al 2003;Chojnacki et al 2009;Theus et al 2010;Silbereis et al 2010). An increased number of GFAP-positive astroglial cells and first beta III-Tubulin-positive neuronal cells were observed at 24 h p-id, which agrees with the findings of Donato et al (2007).…”

Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain

“…The EGL can be considered as a germinal layer, because it is formed by tangential subpial displacement of cell precursors from the germinal trigone of the fourth ventricle that persists during the first 2 postnatal weeks. Some neural precursors in the EGL also express GFAP as reported in the adult SVZ (Silbereis et al 2010). This transitory germinal zone, after radial, centripetal migration of granule cell precursors, progressively reduces its thickness, then disappears at specific ages in different species (from 3 wk in mice to 11 mo in humans, which is very early compared with the onset of puberty [Ponti et al , 2010).…”