Journal article
Cell autonomy of DSCAM function in retinal development
Developmental biology, Vol.361(2), pp.326-337
01/15/2012
Handle:
https://hdl.handle.net/2376/115047
PMCID: PMC3246579
PMID: 22063212
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.
► Conditional allele developed to test DSCAM cell autonomy. ► DSCAM‐mediated processes were genetically separated and are distinct. ► Dscam regulates developmental cell death and spacing in a dose dependent manner. ► DSCAM deficient cells induce mutant phenotype on adjacent homotypic wild type cells. ► DSCAM mediates arborization and spacing by acting within cell types.
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Details
- Title
- Cell autonomy of DSCAM function in retinal development
- Creators
- Peter G Fuerst - Department of Biological Sciences and WWAMI Medical Education Program, University of Idaho, Moscow, ID 83844, USAFreyja Bruce - The University of Aberdeen, Aberdeen, UKRyan P Rounds - Department of Biological Sciences and WWAMI Medical Education Program, University of Idaho, Moscow, ID 83844, USALynda Erskine - The University of Aberdeen, Aberdeen, UKRobert W Burgess - The Jackson Laboratory, Bar Harbor, ME 04609, USA
- Publication Details
- Developmental biology, Vol.361(2), pp.326-337
- Academic Unit
- Center for Reproductive Biology
- Publisher
- Elsevier Inc
- Identifiers
- 99900548074501842
- Language
- English
- Resource Type
- Journal article