Samd7 preserves cell identity and enforces the 'one neuron-one receptor' rule in vertebrate photoreceptors [5dpf_whole_eye]

The exclusive expression of single sensory receptors in individual neurons (the 'one-neuron-one receptor' rule) is essential for vision and other sensory systems. Here, we show that the transcriptional corepressor Samd7 enforces this rule in vertebrate red cones and acts in other photoreceptor types to maintain cell identity. In the zebrafish samd7-/- retina, red cones are transformed to hybrid red/UV-sensitive cones, green cones are transfated to blue cones, and the number of rods is greatly reduced. In the mouse Samd7-/- retina, dorsal M-cones are transformed to hybrid M/S-cones—analogous to the transformation of red to red/UV cones that occurs in zebrafish—and rods aberrantly express cone genes including S-opsin. Altogether, Samd7 acts to repress short-wavelength cone gene expression in long-wavelength-sensitive cones, thereby sustaining the mutually exclusive patterns of opsin expression and cone identity required for color vision. Overall design: To perform RNA-seq on 5-dpf larvae, samd7stl888/+ heterozygotes were intercrossed to produce mixed genotype offspring. Larvae were euthanized by exposure to tricaine, anterior halves of the body were collected in RNAlater (Invitrogen) and stored at 4°C, and corresponding posterior halves were collected in 50 mM NaOH for genotyping. Once genotypes were confirmed, eyes were dissected from the anterior body halves. The eyes from an individual larva constituted one replicate. Three WT and samd7stl888/stl888 replicates were collected and RNA-extracted using the RNeasy Micro Kit (Qiagen), then DNAse-treated and repurified using the Rneasy MinElute Cleanup Kit (Qiagen). RNA concentrations ranged from 1.5-2.2 ng/µl (~20 ng RNA total), with prominent 18/28S peaks and minimal RNA degradation in Bioanalyzer traces.