Samd7 preserves cell identity and enforces the ‘one neuron-one receptor’ rule in vertebrate photoreceptors [adult]

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. To perform RNA-seq on 3 month-old adult retinas, samd7stl888/+ heterozygotes were intercrossed to produce mixed genotype offspring and grown to adulthood. After adults were genotyped, pairs of retinas from three male WT and samd7stl888/stl888 zebrafish were dissected. The pair of retinas from an individual zebrafish were then combined to make one replicate, and RNA was extracted using the RNEasy Mini Kit (Qiagen) with on-column DNAse treatment using the Rnase-Free Dnase Set (Qiagen). RNA concentrations ranged from 20-37 ng/µl (600-1100 ng total), with RIN scores ranging from 9-9.5; there was minimal RNA degradation as shown by Bioanalyzer traces.