Oel A Phillip, Neil Gavin J, Dong Emily M, Balay Spencer D, Collett Keon, Allison W Ted
Department of Biological Sciences, University of Alberta, Edmonton AB, T7Y 1C4, Canada.
Department of Medical Genetics, University of Alberta, Edmonton AB, T6G 2R3, Canada.
iScience. 2020 Nov 15;23(12):101805. doi: 10.1016/j.isci.2020.101805. eCollection 2020 Dec 18.
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 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 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.
转录因子NRL（神经视网膜亮氨酸拉链）已被奉为视网膜中光感受器细胞命运的主要调节因子。在小鼠中，NRL对于确定视杆细胞命运和排除视锥细胞命运是必要且充分的。通过对斑马鱼进行基因工程改造，我们测试了NRL的功能在哺乳动物之外或夜行性物种之外是否具有保守作用，即在具有更丰富和更典型视锥细胞亚型多样性的脊椎动物中。来自斑马鱼或小鼠的Nrl转基因表达足以诱导视杆光感受器细胞。斑马鱼突变体在幼体阶段缺乏视杆细胞（并且有过量的对紫外线敏感的视锥细胞）；因此，小鼠和斑马鱼之间Nrl功能的保守性似乎是合理的。然而，令人惊讶的是，成年Nrl基因敲除突变体斑马鱼中视杆细胞丰富。尽管检测不到Nrl蛋白，但视杆细胞在成年期仍能发育。因此，一条尚未揭示的独立于Nrl的非经典途径能够确定一些视杆光感受器的命运。
