title: Deterministic progenitor behavior and unitary production of neurons in the neocortex.
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.
authors.affiliation: 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.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Postiglione
authors.affiliation: 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.
authors.forename: Teresa G
authors.initials: TG
authors.lastname: Krieger
authors.affiliation: 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.
authors.forename: Luisirene
authors.initials: L
authors.lastname: Hernandez
authors.affiliation: Departments of Biomedical Informatics and Electrical and Computer Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Software, Nankai University, 94 Weijin Road, Tianjin 300071, P.R.C.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Han
authors.affiliation: Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria.
authors.forename: Carmen
authors.initials: C
authors.lastname: Streicher
authors.affiliation: Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Papusheva
authors.affiliation: 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.
authors.forename: Ryan
authors.initials: R
authors.lastname: Insolera
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Kritika
authors.initials: K
authors.lastname: Chugh
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Oren
authors.initials: O
authors.lastname: Kodish
authors.affiliation: Departments of Biomedical Informatics and Electrical and Computer Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Simons
authors.affiliation: Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
authors.affiliation: Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria. Electronic address: simon.hippenmeyer@ist.ac.at.
authors.forename: Simon
authors.initials: S
authors.lastname: Hippenmeyer
authors.affiliation: 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.
authors.forename: Song-Hai
authors.initials: SH
authors.lastname: Shi
mesh_terms: D000818:Animals; D051379:Mice; D019579:Neocortex / Q000166:cytology*; D055495:Neurogenesis; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051857:Otx Transcription Factors / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods; D013234:Stem Cells / Q000378:metabolism
chemical_list: D051857:Otx Transcription Factors; C497656:Otx1 protein, mouse