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K. Alvarez-Delfin, A. C. Morris, J. T. Gamse, J. M. Fadool; Cell Autonomous Function of a T-Box Transcription Factor in Photoreceptor Subtype Specification in Zebrafish. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1268. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
We identified the locus, lot-of-rods (lor), in a screen of chemically mutagenized zebrafish. Retinas of lor mutants display an increased number of rods and a reduced number of ultraviolet sensitive (UV) cones compared to wild type larvae. This phenotype is the opposite of that observed in enhanced S-cone syndrome and the rd7 mouse. The goals of this study are to further characterize the lor mutant phenotype and molecularly identify the mutant gene.
To characterize the photoreceptor phenotype, the number and distribution of the cones and rods in wild type and lor mutant larvae were spatially analyzed. Linkage analysis and complementation testing were used to identify the mutated gene. Cell autonomy was tested by generating genetic chimeras by blastula cell transplants.
Quantitative analysis and spatial distribution of UV cones and rods in lor and wild type retinas suggest an approximate one-to-one exchange of UV cones for rods in the mutant retina. Linkage analysis and complementation testing indicate that the lor locus encodes a T-box transcription factor. Consistent with the proposed role as a transcription factor, lor acted cell-autonomously. In genetic chimeras, lor mutant cells failed to generate UV cones in a wild type host. Conversely, wild type cells displayed the capacity to differentiate into UV cones when transplanted into a mutant host.
These data identify a previously unrecognized function for a T-box transcription factor in photoreceptor subtype specification. Future investigations are aimed at identifying putative interactions with or down stream transcriptional targets of the T-box transcription factor.
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