Neuron
Volume 97, Issue 3, 7 February 2018, Pages 520-537.e6
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Article
A Translational Repression Complex in Developing Mammalian Neural Stem Cells that Regulates Neuronal Specification

https://doi.org/10.1016/j.neuron.2017.12.045Get rights and content
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Highlights

  • Radial precursors are transcriptionally primed to make diverse neuronal subtypes

  • The 4E-T repressor forms a complex with Pum2 during neurogenesis

  • Neuronal specification mRNAs are translationally repressed in radial precursors

  • Disruption of the Pum2/4E-T complex causes misspecification of cortical neurons

Summary

The mechanisms instructing genesis of neuronal subtypes from mammalian neural precursors are not well understood. To address this issue, we have characterized the transcriptional landscape of radial glial precursors (RPs) in the embryonic murine cortex. We show that individual RPs express mRNA, but not protein, for transcriptional specifiers of both deep and superficial layer cortical neurons. Some of these mRNAs, including the superficial versus deep layer neuron transcriptional regulators Brn1 and Tle4, are translationally repressed by their association with the RNA-binding protein Pumilio2 (Pum2) and the 4E-T protein. Disruption of these repressive complexes in RPs mid-neurogenesis by knocking down 4E-T or Pum2 causes aberrant co-expression of deep layer neuron specification proteins in newborn superficial layer neurons. Thus, cortical RPs are transcriptionally primed to generate diverse types of neurons, and a Pum2/4E-T complex represses translation of some of these neuronal identity mRNAs to ensure appropriate temporal specification of daughter neurons.

Keywords

cortex
development
neural stem cells
neurogenesis
radial precursors
neuronal subtype specification
translational repression
Pumilio
4E-T
RNA-binding protein

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Present address: HS2229, 3330 Hospital Drive N.W., University of Calgary, Calgary, AB T2N 1N4, Canada

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Present address: 8-32 Medical Sciences Building, University of Alberta, Edmonton, AB T6G 2H7, Canada

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