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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

Neocortical Excitatory Neuron Clones Labeled Using Nestin-CreERT2/MADM, Related to Figure 2(A) Confocal images of a green/red G2-X clone (top) and a yellow clone (bottom) in a P21 brain treated with TM at E11. Arrowheads indicate glial cells. A high magnification image of labeled neurons and glia (broken lines) is shown as an inset. Scale bars: 100 μm.(B) Quantification of the clone size (E10, n = 5; E11, n = 21; E12, n = 21). Data are presented as mean ± SEM. (∗p < 0.05; ∗∗∗∗p < 0.0001).(C) Percentage of symmetric proliferative division versus asymmetric neurogenic division at different embryonic stages.(D) Quantification of the size of asymmetric neurogenic clones (n = 19). Data are presented as mean ± SEM.
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figs4: Neocortical Excitatory Neuron Clones Labeled Using Nestin-CreERT2/MADM, Related to Figure 2(A) Confocal images of a green/red G2-X clone (top) and a yellow clone (bottom) in a P21 brain treated with TM at E11. Arrowheads indicate glial cells. A high magnification image of labeled neurons and glia (broken lines) is shown as an inset. Scale bars: 100 μm.(B) Quantification of the clone size (E10, n = 5; E11, n = 21; E12, n = 21). Data are presented as mean ± SEM. (∗p < 0.05; ∗∗∗∗p < 0.0001).(C) Percentage of symmetric proliferative division versus asymmetric neurogenic division at different embryonic stages.(D) Quantification of the size of asymmetric neurogenic clones (n = 19). Data are presented as mean ± SEM.

Mentions: Similar results in excitatory neuron clonal labeling and properties were obtained when we used Nestin-CreERT2 (Figure S4), another transgenic mouse line with neural progenitor-specific expression of TM-inducible Cre (Imayoshi et al., 2006). Notably, we occasionally observed labeled neocortical interneurons in Nestin-CreERT2;MADM brains that were readily distinguished based on morphology.


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)

Neocortical Excitatory Neuron Clones Labeled Using Nestin-CreERT2/MADM, Related to Figure 2(A) Confocal images of a green/red G2-X clone (top) and a yellow clone (bottom) in a P21 brain treated with TM at E11. Arrowheads indicate glial cells. A high magnification image of labeled neurons and glia (broken lines) is shown as an inset. Scale bars: 100 μm.(B) Quantification of the clone size (E10, n = 5; E11, n = 21; E12, n = 21). Data are presented as mean ± SEM. (∗p < 0.05; ∗∗∗∗p < 0.0001).(C) Percentage of symmetric proliferative division versus asymmetric neurogenic division at different embryonic stages.(D) Quantification of the size of asymmetric neurogenic clones (n = 19). Data are presented as mean ± SEM.
© Copyright Policy
Related In: Results  -  Collection

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

figs4: Neocortical Excitatory Neuron Clones Labeled Using Nestin-CreERT2/MADM, Related to Figure 2(A) Confocal images of a green/red G2-X clone (top) and a yellow clone (bottom) in a P21 brain treated with TM at E11. Arrowheads indicate glial cells. A high magnification image of labeled neurons and glia (broken lines) is shown as an inset. Scale bars: 100 μm.(B) Quantification of the clone size (E10, n = 5; E11, n = 21; E12, n = 21). Data are presented as mean ± SEM. (∗p < 0.05; ∗∗∗∗p < 0.0001).(C) Percentage of symmetric proliferative division versus asymmetric neurogenic division at different embryonic stages.(D) Quantification of the size of asymmetric neurogenic clones (n = 19). Data are presented as mean ± SEM.
Mentions: Similar results in excitatory neuron clonal labeling and properties were obtained when we used Nestin-CreERT2 (Figure S4), another transgenic mouse line with neural progenitor-specific expression of TM-inducible Cre (Imayoshi et al., 2006). Notably, we occasionally observed labeled neocortical interneurons in Nestin-CreERT2;MADM brains that were readily distinguished based on morphology.

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