Fate-Restricted Neural Progenitors in the Mammalian Cerebral Cortex

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Science  10 Aug 2012:
Vol. 337, Issue 6095, pp. 746-749
DOI: 10.1126/science.1223616

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Generating the Cortex

During development of the cerebral cortex, radial glial neural progenitor cells generate layer-specific subtypes of excitatory neurons in a defined temporal sequence, in which deep layers are formed before upper layers. The prevailing model for cortical neurogenesis over the last 20 years has been the common progenitor model, which proposes that the neurogenic potential of the radial glial cell is progressively restricted over time. In contrast to this model, Franco et al. (p. 746) now show that, in mice, two radial glial cell subtypes appear to be specified at the onset of cortical development: one for neurons of the evolutionarily older lower cortical layers and a second for the upper cortical layers that are present in placental mammals and are enlarged in primates, especially humans.


During development of the mammalian cerebral cortex, radial glial cells (RGCs) generate layer-specific subtypes of excitatory neurons in a defined temporal sequence, in which lower-layer neurons are formed before upper-layer neurons. It has been proposed that neuronal subtype fate is determined by birthdate through progressive restriction of the neurogenic potential of a common RGC progenitor. Here, we demonstrate that the murine cerebral cortex contains RGC sublineages with distinct fate potentials. Using in vivo genetic fate mapping and in vitro clonal analysis, we identified an RGC lineage that is intrinsically specified to generate only upper-layer neurons, independently of niche and birthdate. Because upper cortical layers were expanded during primate evolution, amplification of this RGC pool may have facilitated human brain evolution.

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