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

Abstract The transcription factor NRL (Neural Retina Leucine-zipper) has been canonized 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. Transgenic expression of Nrl from zebrafish or mouse was sufficient to induce rod photoreceptor cells. 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. 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.