Cell autonomy of DSCAM function in retinal development

Peter G Fuerst, Freyja Bruce, Ryan P Rounds, Lynda Erskine, Robert W Burgess

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Cell adhesion molecules (CAMs) provide identifying cues by which neural architecture is sculpted. The Down Syndrome Cell Adhesion Molecule (DSCAM) is required for many neurodevelopmental processes in different species and also has several potential mechanisms of activity, including homophilic adhesion, homophilic repulsion and heterophilic interactions. In the mouse retina, Dscam is expressed in many, but not all neuronal subtypes. Mutations in Dscam cause the fasciculation of dendrites of neighboring homotypic neurons, indicating a role in self-avoidance among cells of a given type, a disruption of the non-random patterning of their cell bodies, and a decrease in developmental cell death in affected cell populations. In order to address how DSCAM facilitates retinal pattering, we developed a conditional allele of Dscam to use alongside existing Dscam mutant mouse strains. Conditional deletion of Dscam reproduces cell spacing, cell number and dendrite arborization defects. Inducible deletion of Dscam and retinal ganglion cell depletion in Brn3b mutant retinas both indicate that these DSCAM-mediated phenotypes can occur independently. In chimeric retinas, in which wild type and Dscam mutant cells are comingled, Dscam mutant cells entangle adjacent wild type cells of the same type, as if both cells were lacking Dscam, consistent with DSCAM-dependent cell spacing and neurite arborization being mediated through homophilic binding cell-to-cell. Deletion of Dscam in specific cell types causes cell-type-autonomous cell body spacing defects, indicating that DSCAM mediates arborization and spacing by acting within given cell types. We also examine the cell autonomy of DSCAM in laminar stratification and find that laminar disorganization can be caused in a non-cell autonomous fashion. Finally, we find Dscam dosage-dependent defects in developmental cell death and amacrine cell spacing, relevant to the increased cell death and other disorders observed in Down syndrome mouse models and human patients, in which Dscam is present in three copies.
Original languageEnglish
Pages (from-to)326-337
Number of pages12
JournalDevelopmental Biology
Volume361
Issue number2
Early online date29 Oct 2011
DOIs
Publication statusPublished - 15 Jan 2012

Fingerprint

Cell Adhesion Molecules
Down Syndrome
Retina
Cell Death
Mutant Strains Mice
Fasciculation
Amacrine Cells
Neuronal Plasticity
Retinal Ganglion Cells
Neurites
Dendrites
Cues
Cell Count

Keywords

  • mosaic
  • adhesion
  • arborization
  • development
  • lamination
  • Down syndrome
  • retinal ganglion cell

Cite this

Cell autonomy of DSCAM function in retinal development. / Fuerst, Peter G; Bruce, Freyja; Rounds, Ryan P; Erskine, Lynda; Burgess, Robert W.

In: Developmental Biology, Vol. 361, No. 2, 15.01.2012, p. 326-337.

Research output: Contribution to journalArticle

Fuerst, PG, Bruce, F, Rounds, RP, Erskine, L & Burgess, RW 2012, 'Cell autonomy of DSCAM function in retinal development', Developmental Biology, vol. 361, no. 2, pp. 326-337. https://doi.org/10.1016/j.ydbio.2011.10.028
Fuerst, Peter G ; Bruce, Freyja ; Rounds, Ryan P ; Erskine, Lynda ; Burgess, Robert W. / Cell autonomy of DSCAM function in retinal development. In: Developmental Biology. 2012 ; Vol. 361, No. 2. pp. 326-337.
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