1. Developmental Biology
Download icon

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 4
  • Views 1,361
  • Annotations
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.

Metrics

  • 1,361
    Page views
  • 297
    Downloads
  • 4
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Developmental Biology
    Feng Wang et al.
    Research Article Updated

    The X-linked gene Rlim plays major roles in female mouse development and reproduction, where it is crucial for the maintenance of imprinted X chromosome inactivation in extraembryonic tissues of embryos. However, while females carrying a systemic Rlim knockout (KO) die around implantation, male Rlim KO mice appear healthy and are fertile. Here, we report an important role for Rlim in testis where it is highly expressed in post-meiotic round spermatids as well as in Sertoli cells. Systemic deletion of the Rlim gene results in lower numbers of mature sperm that contains excess cytoplasm, leading to decreased sperm motility and in vitro fertilization rates. Targeting the conditional Rlim cKO specifically to the spermatogenic cell lineage largely recapitulates this phenotype. These results reveal functions of Rlim in male reproduction specifically in round spermatids during spermiogenesis.

    1. Developmental Biology
    2. Neuroscience
    Hiroki Takechi et al.
    Research Article

    Transmembrane protein Golden goal (Gogo) interacts with atypical cadherin Flamingo to direct R8 photoreceptor axons in the Drosophila visual system. However, the precise mechanisms underlying Gogo regulation during columnar- and layer-specific R8 axon targeting are unknown. Our studies demonstrated that the insulin secreted from surface and cortex glia switches the phosphorylation status of Gogo, thereby regulating its two distinct functions. Non-phosphorylated Gogo mediates the initial recognition of the glial protrusion in the center of the medulla column, whereas phosphorylated Gogo suppresses radial filopodia extension by counteracting Flamingo to maintain a one axon to one column ratio. Later, Gogo expression ceases during the midpupal stage, thus allowing R8 filopodia to extend vertically into the M3 layer. These results demonstrate that the long- and short-range signaling between the glia and R8 axon growth cones regulates growth cone dynamics in a stepwise manner, and thus shape the entire organization of the visual system.