Deterministic progenitor behavior and unitary neuron production in the neocortex
Postiglione, Maria P
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Gao, P., Postiglione, M. P., Krieger, T., Hernandez, L., Wang, C., Han, Z., Streicher, C., et al. (2014). Deterministic progenitor behavior and unitary neuron production in the neocortex. Cell, 159 775-788. https://doi.org/10.1016/j.cell.2014.10.027
Radial glial progenitors (RGPs) are responsible for producing nearly all neocortical neurons, yet a precise understanding of RGP division and neuron production is lacking. Here, we quantitatively analyzed excitatory neuron genesis in the mouse neocortex using Mosaic Analysis with Double Markers (MADM), which provides unprecedented single-cell resolution of progenitor division pattern and potential in vivo. We found that RGPs progress sequentially 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 neuron loss, and a net neuronal unit size reduction. Moreover, about 1/6 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.
This work was supported by the European Union (FP7-CIG618444 to S.H.), the Simons Foundation (to S.-H.S.), NIH grants (R01DA024681 and R01MH101382 to S.-H.S., R01NS050835 to L.L., and T32HD060600 to L.H.), the Wellcome Trust (098357/Z/12/Z to B.D.S.) and the Human Frontier Science Program (RGP0053 to S.-H.S., S.H., B.D.S. and K.H.). L.L. is an investigator of the Howard Hughes Medical Institute.
WELLCOME TRUST (098357/Z/12/Z)
Human Frontier Science Program (HFSP) (RGP0053/2014)
Wellcome Trust (092096/Z/10/Z)
External DOI: https://doi.org/10.1016/j.cell.2014.10.027
This record's URL: https://www.repository.cam.ac.uk/handle/1810/246217
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/