1. Developmental Biology
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Upregulation of neurovascular communication through filamin abrogation promotes ectopic periventricular neurogenesis

  1. Shauna L Houlihan
  2. Alison A Lanctot
  3. Yan Guo
  4. Yuanyi Feng  Is a corresponding author
  1. Northwestern University Feinberg School of Medicine, United States
Research Article
  • Cited 5
  • Views 1,402
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Cite this article as: eLife 2016;5:e17823 doi: 10.7554/eLife.17823

Abstract

Neuronal fate-restricted intermediate progenitors (IPs) are derived from the multipotent radial glia (RGs) and serve as the direct precursors for cerebral cortical neurons, but factors that control their neurogenic plasticity remain elusive. Here we report that IPs' neuron production is enhanced by abrogating filamin function, leading to the generation of periventricular neurons independent of normal neocortical neurogenesis and neuronal migration. Loss of Flna in neural progenitor cells (NPCs) led RGs to undergo changes resembling epithelial-mesenchymal transition (EMT) along with exuberant angiogenesis that together changed the microenvironment and increased neurogenesis of IPs. We show that by collaborating with β-arrestin, Flna maintains the homeostatic signaling between the vasculature and NPCs, and loss of this function results in escalated Vegfa and Igf2 signaling, which exacerbates both EMT and angiogenesis to further potentiate IPs' neurogenesis. These results suggest that the neurogenic potential of IPs may be boosted in vivo by manipulating Flna-mediated neurovascular communication.

Article and author information

Author details

  1. Shauna L Houlihan

    Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Alison A Lanctot

    Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yan Guo

    Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yuanyi Feng

    Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States
    For correspondence
    yuanyi-feng@northwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2793-3962

Funding

National Institute of Neurological Disorders and Stroke (R01NS087575)

  • Yuanyi Feng

Brain Research Foundation

  • Yuanyi Feng

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the experimental mice were handled according to the animal protocol (#IS0001492) approved by institutional animal care and use committee (IACUC) of Northwestern University.

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Publication history

  1. Received: May 13, 2016
  2. Accepted: September 23, 2016
  3. Accepted Manuscript published: September 24, 2016 (version 1)
  4. Version of Record published: October 4, 2016 (version 2)

Copyright

© 2016, Houlihan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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