Nrl is dispensable for specification of rod photoreceptors in adult zebrafish contrasting a deeply conserved requirement earlier in ontogeny

Abstract

AbstractThe transcription factor NRL (Neural Retinal Leucine-zipper) has been canonized, appropriately enough, as the master regulator of photoreceptor cell fate in the retina. NRL is necessary and sufficient to specify rod cell fate and to preclude cone cell fate in mice. By engineering zebrafish we tested if NRL function has conserved roles beyond mammals or beyond nocturnal species, i.e. in a vertebrate possessing a greater and more typical diversity of cone sub-types. Here, transgenic expression of a Nrl homolog from zebrafish or mouse was sufficient to convert developing zebrafish cones into rod photoreceptors. Zebrafish nrl-/- mutants lacked rods (and had excess UV-sensitive cones) as young larvae, thus the conservation of Nrl function between mice and zebrafish appears sound. These data inform hypotheses of photoreceptor evolution through the Nocturnal Bottleneck, suggesting that a capacity to favor nocturnal vision is a property of NRL that predates the emergence of early mammals. Strikingly, however, rods were abundant in adult nrl-/- null mutant zebrafish. Rods developed in adults despite Nrl protein being undetectable. Therefore a yet-to-be-revealed non-canonical pathway independent of nrl is able to specify the fate of some rod photoreceptors.Highlights- Nrl is conserved and sufficient to specify rod photoreceptors in zebrafish retina- Nrl is necessary for rod photoreceptors in early ontogeny of zebrafish larvae- Zebrafish Nrl is functionally conserved with mouse and human NRL- Remarkably, Nrl is dispensable for rod specification in adult zebrafish