Abstract
SummaryRadial glial progenitors (RGPs) are responsible for producing nearly all neocortical neurons. To gain insight into the patterns of RGP division and neuron production, we quantitatively analyzed excitatory neuron genesis in the mouse neocortex using Mosaic Analysis with Double Markers, which provides single-cell resolution of progenitor division patterns and potential in vivo. We found that RGPs progress through a coherent program in which their proliferative potential diminishes in a predictable manner. Upon entry into the neurogenic phase, individual RGPs produce ∼8–9 neurons distributed in both deep and superficial layers, indicating a unitary output in neuronal production. Removal of OTX1, a transcription factor transiently expressed in RGPs, results in both deep- and superficial-layer neuron loss and a reduction in neuronal unit size. Moreover, ∼1/6 of neurogenic RGPs proceed to produce glia. These results suggest that progenitor behavior and histogenesis in the mammalian neocortex conform to a remarkably orderly and deterministic program.
Highlights
The mammalian neocortex commands all higher-order brain functions
We found that Radial glial progenitors (RGPs) progress through a coherent program in which their proliferative potential diminishes in a predictable manner
Removal of OTX1, a transcription factor transiently expressed in RGPs, results in both deep- and superficial-layer neuron loss and a reduction in neuronal unit size
Summary
The mammalian neocortex commands all higher-order brain functions. It consists of an extraordinarily large number of excitatory and inhibitory neurons organized into distinct laminae. Consecutive waves of neurogenesis lead to the formation of cortical layers in an ‘‘inside-out’’ fashion; that is, late-born neurons migrate past early-born neurons and progressively occupy more superficial layers (Angevine and Sidman, 1961). These studies have outlined a framework for our understanding of neocortical neurogenesis, precise knowledge of neuron production and organization, especially at the single-progenitor level, remains elusive
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