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

Autor:	Letelier J; Centro Andaluz de Biología del Desarrollo (CSIC/UPO/JA), Sevilla, Spain.; Centre for Integrative Biology, Facultad de Ciencias, Universidad Mayor, Santiago, Chile., Buono L; Centro Andaluz de Biología del Desarrollo (CSIC/UPO/JA), Sevilla, Spain.; IRCCS SYNLAB SDN, Via E. Gianturco, Naples, Italy., Almuedo-Castillo M; Centro Andaluz de Biología del Desarrollo (CSIC/UPO/JA), Sevilla, Spain., Zang J; Department of Molecular Life Sciences, University of Zürich, Zürich, Switzerland., Mounieres C; Centre for Integrative Biology, Facultad de Ciencias, Universidad Mayor, Santiago, Chile., González-Díaz S; Centro Andaluz de Biología del Desarrollo (CSIC/UPO/JA), Sevilla, Spain., Polvillo R; Centro Andaluz de Biología del Desarrollo (CSIC/UPO/JA), Sevilla, Spain., Sanabria-Reinoso E; Centro Andaluz de Biología del Desarrollo (CSIC/UPO/JA), Sevilla, Spain., Corbacho J; Centro Andaluz de Biología del Desarrollo (CSIC/UPO/JA), Sevilla, Spain., Sousa-Ortega A; Centro Andaluz de Biología del Desarrollo (CSIC/UPO/JA), Sevilla, Spain., Diez Del Corral R; Champalimaud Research, Champalimaud Centre for the Unknown, Lisbon, Portugal., Neuhauss SCF; Department of Molecular Life Sciences, University of Zürich, Zürich, Switzerland., Martínez-Morales JR; Centro Andaluz de Biología del Desarrollo (CSIC/UPO/JA), Sevilla, Spain.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 May 25; Vol. 12. Date of Electronic Publication: 2023 May 25.
DOI:	10.7554/eLife.85594
Abstrakt:	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 ( vsx KO) in zebrafish. Our electrophysiological and histological analyses indicate severe visual impairment and bipolar cells depletion in vsx KO 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 vsx KO 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. Competing Interests: JL, LB, MA, JZ, CM, SG, RP, ES, JC, AS, RD, SN, JM No competing interests declared (© 2023, Letelier, Buono et al.)
Databáze:	MEDLINE
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