Abstract
Radial glia of the mouse cerebral cortex emerge from neuroepithelial stem cells around embryonic day 11 and produce excitatory cortical neurons until a few days before birth. The molecular mechanisms that regulate the end of cortical neurogenesis remain largely unknown. Here we investigated if the Dicer-dependent microRNA (miRNA) pathway is involved. By electroporating a cre-recombinase expression vector into the cortex of E13.5 embryos carrying a conditional allele of Dicer1, we induced mosaic recombination causing Dicer1 deletion and reporter activation in a subset of radial glia. We analysed the long-term fates of their progeny. We found that mutant radial glia produced abnormally large numbers of Cux1-positive neurons, many of which populated the superficial cortical layers. Injections of the S-phase marker bromodeoxyuridine between postnatal days 3 and 14 showed that much of this population was generated postnatally. Our findings suggest a role for Dicer-dependent processes in limiting the timespan of cortical neurogenesis.
Highlights
Radial glia are a class of undifferentiated cerebral cortical progenitor cells that give rise to excitatory neurons and astrocytes (Miyata et al, 2001, 2010; Noctor et al, 2001; Okano and Temple, 2009; Voigt, 1989)
We examined the GFPþ cells in postnatal day 14 (P14) brains, which were found in the subventricular zone (SVZ), along the white matter (WM) and in the cortex (Ctx) in both genotypes (Fig. 4A), for persistent co-expression of makers of progenitors and immature neurons
In this study we analysed a model of mosaic deletion of Dicer in a subset of radial glia and found an abnormally large population of cortical neurons generated outside the normal time-window of cortical neurogenesis
Summary
Radial glia are a class of undifferentiated cerebral cortical progenitor cells that give rise to excitatory neurons and astrocytes (Miyata et al, 2001, 2010; Noctor et al, 2001; Okano and Temple, 2009; Voigt, 1989). Cortical neurogenesis in the mouse normally occurs between E11 and E17, after which radial glia generate mainly astrocytes (Caviness, 1982; Gillies and Price, 1993; Levers et al, 2001; Takahashi et al, 1995). It is likely that modifications to the molecular mechanisms controlling the timing of the switch from radial glial neurogenesis to gliogenesis were instrumental in neocortical evolution. Hairpins containing mature miRNAs n Correspondence to: The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA
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