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

Abstract

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.

Comparative single-cell transcriptomic analysis reveals putative differentiation drivers and potential origin of vertebrate retina

“…In HCs, the activity of lhx1a was confirmed 38 and hmx2, hmx3a were identified as novel regulators. In BCs, vsx1 39 , dmbx1a and rorab were active. Our analysis confirmed the activity of thrb and crx in cones and nrl in rods, wherein we also identified a novel regulator, mafba.…”

Retinal Degeneration Response to Graphene Quantum Dots: Disruption of the Blood–Retina Barrier Modulated by Surface Modification-Dependent DNA Methylation

“…The proper development of the eyes is governed by a morphogenetic process that necessitates accurate spatial and temporal gene regulation. Disruption in the initial stages of eye organogenesis leads to the cessation of eye development or multiple eye tissue disorders with the degeneration of the retina being a prominent issue. , The characteristic markers for the specific subclasses of morphogenesis and cell differentiation are mentioned: RPE ( pax6a and six3b ), , photoreceptor cells of the ONL ( opn1sw1 , arr3b , and opn1lw1 ), , glial ( gfap ), and bipolar cells ( vsx1 ) of the INL layer and ganglion cells ( tenm3 ) of the GCL layer . These were accessed to corroborate the interference with the GQDs.…”

In Search of a Target Gene for a Desirable Phenotype in Aquaculture: Genome Editing of Cyprinidae and Salmonidae Species

“…Much of the work has focused on the role of specific genes in organ formation and function, including the lens [ 99 ], retina [ 100 , 101 , 102 ], optic neurons [ 103 , 104 ], ocular vessels [ 105 , 106 ], inner ear [ 107 , 108 , 109 , 110 , 111 ], vestibular apparatus [ 111 ], otoliths [ 112 ], brain [ 89 , 113 , 114 , 115 , 116 , 117 ], neural tissue [ 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 ] and nervous system [ 128 , 129 , 130 ], heart [ 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 ], cardiomyocytes [ 140 , 141 , 142 , 143 ], including cardiovascular rate control [ 144 , 145 ], blood vessels [ 146 , 147 ,…”