Abstract
SummaryThe 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.
Highlights
Rods and cones are the ciliary photoreceptors used by vertebrates to enable vision across a broad range of circumstances
We tested if neural retina leucine zipper (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
A yet-to-be-revealed non-canonical pathway independent of Nrl is able to specify the fate of some rod photoreceptors
Summary
Rods and cones are the ciliary photoreceptors used by vertebrates to enable vision across a broad range of circumstances. Rod photoreceptors enable vision in dim conditions, while cone photoreceptors convey wavelength-specific information, enable high acuity, and can operate in brightly lit environments Retinas with both rods and cones are known as duplex retinas, and the basic features of the duplex retina are present even among some of the earliest branching vertebrates, the lampreys (Asteriti et al, 2015; Collin and Trezise, 2004; Morshedian and Fain, 2015). Without THRB activity, it becomes a short wavelength (UV/blue) light-sensitive S-cone (the ancestral UV cone expressing SWS1 opsin) (Ng et al, 2001) This efficient two-factor specification model is expected to be sufficient to generate all photoreceptor diversity in most all eutherian mammals, which have lost the ancestral blue and green light-sensitive cone subtypes (Ng et al, 2011). Homologs of NRL have not been disrupted or manipulated sufficiently to appreciate its role(s) in species outside of mammals
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