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Q. Ding, L. Gan; Mbh1 Regulates Differentiation and Survival of Ganglion and Amacrine Cells in the Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5402.
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© ARVO (1962-2015); The Authors (2016-present)
BarH/Barhl is a family of homeobox-containing genes with important roles in decisions of cell fate, migration and survival. These proteins exert transcriptional regulation by either repression or activation mechanisms. Mbh1, a member of Bar gene family is robustly expressed in the developing central nervous system. In the retina, Mbh1 is expressed by retinal ganglion cells (RGCs), amacrine cells and horizontal cells. In this study, the author investigated the in vivo role of Mbh1 in the development of retina and the genetic cascade.
Mbh1 knockout mice were generated. Using co-immunolabeling and in situ hybridization techniques, the expression of cell-type and subtype specific markers for various neurons, as well as other transcription regulators of retinal neuron differentiation was examined in the developing and mature retinas.
In Mbh1-null retina, amacrine cells are significantly reduced in both glycinergic and GABAergic subtypes; while another subtype, cholinergic amacrine cells are greatly increased. Additionally, targeted deletion of Mbh1 does not affect RGCs formation but leads to a loss of RGCs from late embryonic stage and caspase3 dependent cell programming death may be involved. This elevated cell apoptosis happens cell-autonomously. The expression of Mbh1 is dramatically reduced in Math5-null retina in both the GCL and INBL where RGCs and amacrine cells reside.
Mbh1 is required for the survival of a subset of RGCs and amacrine cells. The increase of cholinergic amacrine cells suggests that Mbh1 may promote the differentiation of cholinergic amacrine cells and play roles in the subtype specification of amacrine cells. Genetic analysis also implies that Mbh1 acts downstream to Math5 to regulate the retina development.
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