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Shuai Li, Peter Fuerst; Analysis of Cell Death Pathways in Developing Retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5134.
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Developmental cell death (DCD) is critical for organization of the retina. DCD in the mouse retina is mediated through a number of factors, including diffusible ligands, like BDNF, and its receptor TrkB, or cell adhesion molecules, including the gamma protocadherin complex and the dscam (Down Syndrome Cell Adhesion Molecule) genes. The purpose of this research project is to test the hypothesis that cell adhesion molecules use conserved signaling pathways mediated by DCD regulatory genes, such as Bax and Bcl-xl.
In this study we utilize conditional mouse alleles of the genes dscam, γ-protocadherin, bax and bcl-xl to map cell death pathways. Our study assayed genes that were differentially expressed in postnatal day zero mouse retina in which each of these genes had been targeted for deletion in retinal ganglion cells by Brn3b-Cre. This research gives insight into which signaling pathways are involved in DCD progress during retinal development. Gene expression was measured by microarray.
A higher degree of DCD is observed in γ-protocadherin and bcl-xl knockout retinas compared to wild type, while a lower degree of DCD is observed in dscam and bax knock out retinas, compared to wild type. Data from microarrays was used to map similarity and differences between changes in gene expression networks when comparing wild type, cell adhesion molecule and mitochondrial factor deficient retinas. Results were confirmed by RT-PCR and immunohistochemistry.
The conditional Dscam knockout phenotype of less DCD in the mouse retina indicates DSCAM in the wild type retina plays a role that promotes DCD in a fashion similar to bax. Likewise γ-protocadhrins and bcl-xl normally promote cell survival in the wild type retina. Analysis of our results indicates the degree to which cell adhesion molecules influence DCD in a similar fashion to mitochondrial factors.
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