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Dynamic mRNA Transport and Local Translation in Radial Glial Progenitors of the Developing Brain.

Publication ,  Journal Article
Pilaz, L-J; Lennox, AL; Rouanet, JP; Silver, DL
Published in: Curr Biol
December 19, 2016

In the developing brain, neurons are produced from neural stem cells termed radial glia [1, 2]. Radial glial progenitors span the neuroepithelium, extending long basal processes to form endfeet hundreds of micrometers away from the soma. Basal structures influence neuronal migration, tissue integrity, and proliferation [3-7]. Yet, despite the significance of these distal structures, their cell biology remains poorly characterized, impeding our understanding of how basal processes and endfeet influence neurogenesis. Here we use live imaging of embryonic brain tissue to visualize, for the first time, rapid mRNA transport in radial glia, revealing that the basal process is a highway for directed molecular transport. RNA- and mRNA-binding proteins, including the syndromic autism protein FMRP, move in basal processes at velocities consistent with microtubule-based transport, accumulating in endfeet. We develop an ex vivo tissue preparation to mechanically isolate radial glia endfeet from the soma, and we use photoconvertible proteins to demonstrate that mRNA is locally translated. Using RNA immunoprecipitation and microarray analyses of endfeet, we discover FMRP-bound transcripts, which encode signaling and cytoskeletal regulators, including many implicated in autism and neurogenesis. We show FMRP controls transport and localization of one target, Kif26a. These discoveries reveal a rich, regulated local transcriptome in radial glia, far from the soma, and establish a tractable mammalian model for studying mRNA transport and local translation in vivo. We conclude that cytoskeletal and signaling events at endfeet may be controlled through translation of specific mRNAs transported from the soma, exposing new mechanistic layers within stem cells of the developing brain.

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Published In

Curr Biol

DOI

EISSN

1879-0445

Publication Date

December 19, 2016

Volume

26

Issue

24

Start / End Page

3383 / 3392

Location

England

Related Subject Headings

  • Transcriptome
  • RNA, Messenger
  • Protein Biosynthesis
  • Protein Binding
  • Mice
  • Gene Expression Regulation, Developmental
  • Fragile X Mental Retardation Protein
  • Ependymoglial Cells
  • Developmental Biology
  • Brain
 

Citation

APA
Chicago
ICMJE
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Pilaz, L.-J., Lennox, A. L., Rouanet, J. P., & Silver, D. L. (2016). Dynamic mRNA Transport and Local Translation in Radial Glial Progenitors of the Developing Brain. Curr Biol, 26(24), 3383–3392. https://doi.org/10.1016/j.cub.2016.10.040
Pilaz, Louis-Jan, Ashley L. Lennox, Jeremy P. Rouanet, and Debra L. Silver. “Dynamic mRNA Transport and Local Translation in Radial Glial Progenitors of the Developing Brain.Curr Biol 26, no. 24 (December 19, 2016): 3383–92. https://doi.org/10.1016/j.cub.2016.10.040.
Pilaz L-J, Lennox AL, Rouanet JP, Silver DL. Dynamic mRNA Transport and Local Translation in Radial Glial Progenitors of the Developing Brain. Curr Biol. 2016 Dec 19;26(24):3383–92.
Pilaz, Louis-Jan, et al. “Dynamic mRNA Transport and Local Translation in Radial Glial Progenitors of the Developing Brain.Curr Biol, vol. 26, no. 24, Dec. 2016, pp. 3383–92. Pubmed, doi:10.1016/j.cub.2016.10.040.
Pilaz L-J, Lennox AL, Rouanet JP, Silver DL. Dynamic mRNA Transport and Local Translation in Radial Glial Progenitors of the Developing Brain. Curr Biol. 2016 Dec 19;26(24):3383–3392.
Journal cover image

Published In

Curr Biol

DOI

EISSN

1879-0445

Publication Date

December 19, 2016

Volume

26

Issue

24

Start / End Page

3383 / 3392

Location

England

Related Subject Headings

  • Transcriptome
  • RNA, Messenger
  • Protein Biosynthesis
  • Protein Binding
  • Mice
  • Gene Expression Regulation, Developmental
  • Fragile X Mental Retardation Protein
  • Ependymoglial Cells
  • Developmental Biology
  • Brain