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Cell. 2014 Nov 6;159(4):775-88. doi: 10.1016/j.cell.2014.10.027.

Deterministic progenitor behavior and unitary production of neurons in the neocortex.

Author information

1
Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Graduate Program in Neuroscience, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
2
Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria.
3
Cavendish Laboratory, Department of Physics, J.J. Thomson Avenue, University of Cambridge, Cambridge CB3 0HE, UK; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
4
Departments of Biomedical Informatics and Electrical and Computer Engineering, The Ohio State University, Columbus, OH 43210, USA.
5
College of Software, Nankai University, 94 Weijin Road, Tianjin 300071, P.R.C.
6
Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
7
Cavendish Laboratory, Department of Physics, J.J. Thomson Avenue, University of Cambridge, Cambridge CB3 0HE, UK; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK.
8
Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA.
9
Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria. Electronic address: simon.hippenmeyer@ist.ac.at.
10
Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Graduate Program in Neuroscience, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA. Electronic address: shis@mskcc.org.

Abstract

Radial 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.

PMID:
25417155
PMCID:
PMC4225456
DOI:
10.1016/j.cell.2014.10.027
[Indexed for MEDLINE]
Free PMC Article

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