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Nature. 2019 Sep;573(7774):370-374. doi: 10.1038/s41586-019-1515-6. Epub 2019 Aug 28.

Temporal plasticity of apical progenitors in the developing mouse neocortex.

Author information

1
Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.
2
Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
3
Institute of Neuroscience, ETH Zürich, Schwerzenbach, Switzerland.
4
Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland. denis.jabaudon@unige.ch.
5
Clinic of Neurology, Geneva University Hospital, Geneva, Switzerland. denis.jabaudon@unige.ch.

Abstract

The diverse subtypes of excitatory neurons that populate the neocortex are born from apical progenitors located in the ventricular zone. During corticogenesis, apical progenitors sequentially generate deep-layer neurons followed by superficial-layer neurons directly or via the generation of intermediate progenitors. Whether neurogenic fate progression necessarily implies fate restriction in single progenitor types is unknown. Here we specifically isolated apical progenitors and intermediate progenitors, and fate-mapped their respective neuronal progeny following heterochronic transplantation into younger embryos. We find that apical progenitors are temporally plastic and can re-enter past molecular, electrophysiological and neurogenic states when exposed to an earlier-stage environment by sensing dynamic changes in extracellular Wnt. By contrast, intermediate progenitors are committed progenitors that lack such retrograde fate plasticity. These findings identify a diversity in the temporal plasticity of neocortical progenitors, revealing that some subtypes of cells can be untethered from their normal temporal progression to re-enter past developmental states.

PMID:
31462778
DOI:
10.1038/s41586-019-1515-6

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