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L. Gan, L. Feng, Z.-H. Xie, Q. Ding, R. Libby; Math5 Controls the Cell Fate Acquisition of Multiple Retinal Neurons. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2524.
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Loss of math5 leads to the absence of retinal ganglion cell (RGC) and concurrently, to an increase in cone and displaced amacrine cells. It remains unclear whether this change in retinal cell composition results from the fate conversion of math5-lineage cells. The purpose of this study is to determine the fate of math5-lineage cells in the absence of math5.
We performed a lineage analysis of math5-expressing cells using the math5-Cre knock-in and conditional GFP reporter (Z/EG) mouse lines. The cells from math5-lineage were permanently marked by the expression of GFP in normal and math5-null retinas, and the identities of these cells were characterized using retinal cell type-specific antibodies.
During normal retinal development, math5-lineage cells mostly give rise to RGCs, GABAergic, cholinergic, and AII amarine cells, horizontal cells, and cone photoreceptors. In the absence of math5, there is an increase of math5-lineage cells becoming cone and rod photoreceptors, cholinergic and AII amacrine subtypes, the displaced amacrine (DA) cells, and bipolar cells. The expression of non-RGC retinogenetic bHLH factors NeuroD and Bhlhb5 is up-regulated. Moreover, loss of math5 results in an increased apoptosis of math5-lineage cells and a decreased postnatal cell proliferation.
The increase of math5-lineage cells becoming non-RGCs in math5-null retinas. The observed cell fate conversion results from the premature expression of non-RGC retinogenetic factors. Together with the observed changes in cell death and proliferation in math5-null retinas, our lineage tracing analysis unveils a comprehensive function of Math5 in the generation of multiple retinal cell types during the retinal development.
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