TY - JOUR TI - Mutation of vsx genes in zebrafish highlights the robustness of the retinal specification network AU - Letelier, Joaquín AU - Buono, Lorena AU - Almuedo-Castillo, María AU - Zang, Jingjing AU - Mounieres, Constanza AU - González-Díaz, Sergio AU - Polvillo, Rocío AU - Sanabria-Reinoso, Estefanía AU - Corbacho, Jorge AU - Sousa-Ortega, Ana AU - Diez del Corral, Ruth AU - Neuhauss, Stephan CF AU - Martínez-Morales, Juan R A2 - Levine, Edward M A2 - Stainier, Didier YR A2 - Harris, William A VL - 12 PY - 2023 DA - 2023/05/25 SP - e85594 C1 - eLife 2023;12:e85594 DO - 10.7554/eLife.85594 UR - https://doi.org/10.7554/eLife.85594 AB - Genetic studies in human and mice have established a dual role for Vsx genes in retina development: an early function in progenitors’ specification, and a later requirement for bipolar-cells fate determination. Despite their conserved expression patterns, it is currently unclear to which extent Vsx functions are also conserved across vertebrates, as mutant models are available only in mammals. To gain insight into vsx function in teleosts, we have generated vsx1 and vsx2 CRISPR/Cas9 double knockouts (vsxKO) in zebrafish. Our electrophysiological and histological analyses indicate severe visual impairment and bipolar cells depletion in vsxKO larvae, with retinal precursors being rerouted toward photoreceptor or Müller glia fates. Surprisingly, neural retina is properly specified and maintained in mutant embryos, which do not display microphthalmia. We show that although important cis-regulatory remodelling occurs in vsxKO retinas during early specification, this has little impact at a transcriptomic level. Our observations point to genetic redundancy as an important mechanism sustaining the integrity of the retinal specification network, and to Vsx genes regulatory weight varying substantially among vertebrate species. KW - vsx genes KW - zebrafish retina KW - medaka retina KW - bipolar cells specification KW - neural retina network KW - CRISPR/Cas9 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -