Cell-Type Specific Roles for PTEN in Establishing a Functional Retinal Architecture

Authors Organisations
  • Robert Cantrup(Author)
    University of Calgary
  • Rajiv Dixit(Author)
    University of Calgary
  • Elena Palmesino(Author)
    Université de Montréal
  • Stephan Bonfield(Author)
    University of Calgary
  • Tarek Shaker(Author)
    University of Calgary
  • Nobuhiko Tachibana(Author)
    University of Calgary
  • Dawn Zinyk(Author)
    University of Calgary
  • Sarah Dalesman(Author)
  • Kazuhiro Yamakawa(Author)
    RIKEN Brain Science Institute (RIKEN BSI)
  • William K. Stell(Author)
    University of Calgary
  • Rachel O. Wong(Author)
    University of Washington
  • Benjamin E. Reese(Author)
    University of California, Santa Barbara
  • Artur Kania(Author)
    Université de Montréal
  • Yves Sauvé(Author)
    University of Alberta
  • Carol Schuurmans(Author)
    University of Calgary
Type Article
Original languageEnglish
Article numbere32795
JournalPLoS One
Issue number3
Publication statusPublished - 05 Mar 2012
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The retina has a unique three-dimensional architecture, the precise organization of which allows for complete sampling of the visual field. Along the radial or apicobasal axis, retinal neurons and their dendritic and axonal arbors are segregated into layers, while perpendicular to this axis, in the tangential plane, four of the six neuronal types form patterned cellular arrays, or mosaics. Currently, the molecular cues that control retinal cell positioning are not well-understood, especially those that operate in the tangential plane. Here we investigated the role of the PTEN phosphatase in establishing a functional retinal architecture.

Methodology/Principal Findings
In the developing retina, PTEN was localized preferentially to ganglion, amacrine and horizontal cells, whose somata are distributed in mosaic patterns in the tangential plane. Generation of a retina-specific Pten knock-out resulted in retinal ganglion, amacrine and horizontal cell hypertrophy, and expansion of the inner plexiform layer. The spacing of Pten mutant mosaic populations was also aberrant, as were the arborization and fasciculation patterns of their processes, displaying cell type-specific defects in the radial and tangential dimensions. Irregular oscillatory potentials were also observed in Pten mutant electroretinograms, indicative of asynchronous amacrine cell firing. Furthermore, while Pten mutant RGC axons targeted appropriate brain regions, optokinetic spatial acuity was reduced in Pten mutant animals. Finally, while some features of the Pten mutant retina appeared similar to those reported in Dscam-mutant mice, PTEN expression and activity were normal in the absence of Dscam.

We conclude that Pten regulates somal positioning and neurite arborization patterns of a subset of retinal cells that form mosaics, likely functioning independently of Dscam, at least during the embryonic period. Our findings thus reveal an unexpected level of cellular specificity for the multi-purpose phosphatase, and identify Pten as an integral component of a novel cell positioning pathway in the retina.