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Transcriptome analysis of the zebrafish atoh7-/- mutant, lakritz, highlights Atoh7-dependent genetic networks with potential implications for human eye diseases

By Giuseppina Covello, Fernando J. Rossello, Michele Filosi, Felipe Gajardo, Anne-Laure Duchemin, Beatrice F Tremonti, Michael Eichenlaub, Jose M. Polo, David Powell, John Ngai, Miguel L. Allende, Enrico Domenici, Mirana Ramialison, Lucia Poggi

Posted 10 Apr 2020
bioRxiv DOI: 10.1101/2020.04.09.033704

Expression of the bHLH transcription protein Atoh7 is a crucial factor conferring competence to retinal progenitor cells for the development of retinal ganglion cells. A number of studies have emerged establishing ATOH7 as a retinal disease gene. Remarkably, such studies uncovered ATOH7 variants associated with global eye defects including optic nerve hypoplasia, microphthalmia, retinal vascular disorders and glaucoma. The complex genetic networks and cellular decisions arising downstream of atoh7 expression, and how their dysregulation cause development of such disease traits remains unknown. To begin to understand such Atoh7-dependent events in vivo we performed transcriptome analysis of wild type and atoh7 mutant (lakritz) zebrafish embryos at the onset of retinal ganglion cell differentiation. We investigated in silico interplays of atoh7 and other disease-related genes and pathways. By network reconstruction analysis of differentially expressed genes we identified gene clusters enriched in retinal development, cell cycle, chromatin remodelling, stress response and Wnt pathways. By weighted gene coexpression network we identified coexpression modules affected by the mutation and enriched in retina development genes tightly connected to atoh7. We established the groundwork whereby Atoh7-linked cellular and molecular processes can be investigated in the dynamic multi- tissue environment of the developing normal and diseased vertebrate eye. ### Competing Interest Statement The authors have declared no competing interest.

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