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Xiuqian Mu, Fuguo Wu, Renzhong Li, Sapkota Darshan, Shengguo Li, Mengqing Xiang, Steven J. Fliesler, Maureen Gannon; Onecut 1 Is Essential For The Genesis Of Retinal Horizontal Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):431.
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© ARVO (1962-2015); The Authors (2016-present)
Previously, we showed that the transcription factor Onecut 1 (Oc1) is expressed in developing horizontal cells (HCs) and ganglion cells (RGCs) in the mouse retina. Like other retinal cell types, during embryonic development, horizontal cells arise from multipotent retinal progenitor cells and their genesis is subject to regulation by transcriptional factors in a hierarchical manner. Here, we further examined the function of Oc1 in mouse retinal development.
We conditionally knocked out Oc1 in the developing mouse retina by crossing an Oc1-flox allele with the Six3-Cre transgenic line and examined the consequences to retinal development, using histological and immunofluorescence methods.
Thickness of the outer nuclear layer in the Oc1-null retina was diminished, relative to age-matched controls. Consistent with this, the majority (~80%) of HCs were absent in the Oc1 knockout mouse retina at both adult and embryonic stages, as determined by immunostaining for HC markers, such as Lim1, Calbindin, NFL, and Pgp9.5, and this reduction was observed as early as E14.5, implying that Oc1 is essential for the initial genesis of horizontal cells. However, neither RGCs nor any of the other retinal cell types were affected, as indicated by the expression of specific markers for those cell types. These results indicate that Oc1 is a novel regulator for horizontal cell formation. Co-labeling showed that Oc1 expression overlapped partially with that of other transcription factors, including FoxN4, Ptf1a, Prox1 and Lim1, required for horizontal cell development. Analysis of the expression of these factors in Oc1-null and FoxN4-null retinas suggested a genetic relationship between Oc1 and other genes, such that Oc1 is downstream of FoxN4, in parallel with Ptf1a, but is upstream of Prox1 and Lim1. Studies are in progress, using electron microscopic, electrophysiological and behavioral methods, to further assess how loss of horizontal cells affects retinal circuitry and vision.
Oc1 plays an essential role in the development of horizontal cells and is part of the gene regulatory hierarchy for horizontal cell formation.
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