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Peter G. Fuerst, Robert Burgess, Li Shuai; Mechanism Of Cam Dependent Cell Death In The Developing Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1955.
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Normal developmental cell death in the developing retina is dependent on cell adhesion molecules including the gamma protocadherins and the Dscam (Down Syndrome Cell Adhesion Molecule) family of cell adhesion molecules. In the absence of Dscams cells that would normally express a given Dscam do not undergo normal developmental cell death during early stages of development, but are more susceptible to cell death at later developmental stages. As a result some cell types are overabundant in the Dscam deficient retina while others are largely absent.
Using mutant mouse alleles, transcriptional profiling and in vitro analysis such as yeast two hybrid we examine the mechanism by which DSCAMs regulates developmental cell death.
Retinal ganglion cells are hypertrophied in the Dscam null retina and are initially overly abundant as a result of decreased developmental cell death. A late wave of cell death reduces some populations of retinal ganglion cells more than others. This decrease is observed in a non-cell autonomous manner suggesting downstream wiring is necessary for normal maintenance of retinal ganglion cells. Analysis of transcriptional changes in mutant retinas suggest involvement of the Akt and PTEN pathways.
Dscams contribute to several aspects of retinal development including arborization, refinement, spacing and cell number. Using a series of mutant mouse alleles we are able to differentiate primary phenotypes from downstream phenotypes.
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