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

Gao P, Postiglione MP, Krieger TG, Hernandez L, Wang C, Han Z, Streicher C, Papusheva E, Insolera R, Chugh K, Kodish O, Huang K, Simons BD, Luo L, Hippenmeyer S, Shi SH - Cell (2014)

Bottom Line: We found that 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.These results suggest that progenitor behavior and histogenesis in the mammalian neocortex conform to a remarkably orderly and deterministic program.

View Article: PubMed Central - PubMed

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.

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.

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Related in: MedlinePlus

Predictable Rate of RGP Transitioning from Neurogenesis to Gliogenesis(A) Confocal images of an E10–P21 green/red G2-X clone that contains both green and red glial cells. High-magnification images of an astrocyte (A’) and a few oligodendrocytes (A’’) are shown in insets. Scale bars, 200 μm and 50 μm.(B) 3D reconstruction image of the clone in (A).(C) Percentage of all clones with or without glia with regard to the number of neurons in the clone.(D) Percentage of asymmetric neurogenic clone with or without glia at P7–P10 and P21–P30.Data are presented as mean ± SEM. See also Figure S7.
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fig7: Predictable Rate of RGP Transitioning from Neurogenesis to Gliogenesis(A) Confocal images of an E10–P21 green/red G2-X clone that contains both green and red glial cells. High-magnification images of an astrocyte (A’) and a few oligodendrocytes (A’’) are shown in insets. Scale bars, 200 μm and 50 μm.(B) 3D reconstruction image of the clone in (A).(C) Percentage of all clones with or without glia with regard to the number of neurons in the clone.(D) Percentage of asymmetric neurogenic clone with or without glia at P7–P10 and P21–P30.Data are presented as mean ± SEM. See also Figure S7.

Mentions: In addition to self-renewal and neuron production, RGPs also give rise to glial cells (Magavi et al., 2012; Qian et al., 2000; Rowitch and Kriegstein, 2010; Schmechel and Rakic, 1979). Consistent with this, we frequently found that spatially isolated clonal clusters induced at E10–E13 contained both neurons and glia, including astrocytes and oligodendrocytes (Figures 7A, 7B, and S7). Notably, although we observed clones with only neurons, we did not detect any clone with only glial cells, suggesting that glia-specific RGPs, if they exist, are extremely scarce and that gliogenesis consistently occurs after neurogenesis at the individual RGP level.


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

Gao P, Postiglione MP, Krieger TG, Hernandez L, Wang C, Han Z, Streicher C, Papusheva E, Insolera R, Chugh K, Kodish O, Huang K, Simons BD, Luo L, Hippenmeyer S, Shi SH - Cell (2014)

Predictable Rate of RGP Transitioning from Neurogenesis to Gliogenesis(A) Confocal images of an E10–P21 green/red G2-X clone that contains both green and red glial cells. High-magnification images of an astrocyte (A’) and a few oligodendrocytes (A’’) are shown in insets. Scale bars, 200 μm and 50 μm.(B) 3D reconstruction image of the clone in (A).(C) Percentage of all clones with or without glia with regard to the number of neurons in the clone.(D) Percentage of asymmetric neurogenic clone with or without glia at P7–P10 and P21–P30.Data are presented as mean ± SEM. See also Figure S7.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4225456&req=5

fig7: Predictable Rate of RGP Transitioning from Neurogenesis to Gliogenesis(A) Confocal images of an E10–P21 green/red G2-X clone that contains both green and red glial cells. High-magnification images of an astrocyte (A’) and a few oligodendrocytes (A’’) are shown in insets. Scale bars, 200 μm and 50 μm.(B) 3D reconstruction image of the clone in (A).(C) Percentage of all clones with or without glia with regard to the number of neurons in the clone.(D) Percentage of asymmetric neurogenic clone with or without glia at P7–P10 and P21–P30.Data are presented as mean ± SEM. See also Figure S7.
Mentions: In addition to self-renewal and neuron production, RGPs also give rise to glial cells (Magavi et al., 2012; Qian et al., 2000; Rowitch and Kriegstein, 2010; Schmechel and Rakic, 1979). Consistent with this, we frequently found that spatially isolated clonal clusters induced at E10–E13 contained both neurons and glia, including astrocytes and oligodendrocytes (Figures 7A, 7B, and S7). Notably, although we observed clones with only neurons, we did not detect any clone with only glial cells, suggesting that glia-specific RGPs, if they exist, are extremely scarce and that gliogenesis consistently occurs after neurogenesis at the individual RGP level.

Bottom Line: We found that 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.These results suggest that progenitor behavior and histogenesis in the mammalian neocortex conform to a remarkably orderly and deterministic program.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus