Mutation of vsx genes in zebrafish highlights the robustness of the retinal specification network

• DOI: 10.7554/elife.85594
• Publication Date: 2023-05-25T09:00:22Z
• Authors: Joaquín Letelier; Lorena Buono; María Almuedo-Cas...; Jingjing Zang; Constanza Mounieres; Sergio González-Díaz; Rocío Polvillo; Estefanía Sanabri...; Jorge Corbacho; Ana Sousa-Ortega; Ruth Diez del Corral; Stephan CF Neuhauss; Juan R Martínez-M...
• Keywords: Electroretinography

Genetic studies in human and mice have established a dual role for Vsx genes retina development: an early function progenitors’ specification, later requirement bipolar-cells fate determination. Despite their conserved expression patterns, it is currently unclear to which extent functions are also across vertebrates, as mutant models available only mammals. To gain insight into vsx teleosts, we generated vsx1 vsx2 CRISPR/Cas9 double knockouts ( KO) zebrafish. Our electrophysiological histological analyses indicate severe visual impairment bipolar cells depletion KO larvae, with retinal precursors being rerouted toward photoreceptor or Müller glia fates. Surprisingly, neural properly specified maintained embryos, do not display microphthalmia. We show that although important cis -regulatory remodelling occurs retinas during this has little impact at transcriptomic level. observations point genetic redundancy mechanism sustaining the integrity of specification network, regulatory weight varying substantially among vertebrate species.