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Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish

Lorena Buono, Silvia Naranjo, Tania Moreno-Marmol, Berta de la Cerda, Rocío Polvillo, View ORCID ProfileFrancisco-Javier Díaz-Corrales, View ORCID ProfileOzren Bogdanovic, Paola Bovolenta, View ORCID ProfileJuan-Ramón Martínez-Morales
doi: https://doi.org/10.1101/2020.05.28.121038
Lorena Buono
1Centro Andaluz de Biología del Desarrollo- CABD (CSIC/UPO/JA), Seville 41013, Spain
2Centro de Biología Molecular “Severo Ochoa,” (CSIC/UAM)
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Silvia Naranjo
1Centro Andaluz de Biología del Desarrollo- CABD (CSIC/UPO/JA), Seville 41013, Spain
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Tania Moreno-Marmol
2Centro de Biología Molecular “Severo Ochoa,” (CSIC/UAM)
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Berta de la Cerda
3Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER (CSIC/US/UPO/JA), Seville 41092, Spain
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Rocío Polvillo
1Centro Andaluz de Biología del Desarrollo- CABD (CSIC/UPO/JA), Seville 41013, Spain
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Francisco-Javier Díaz-Corrales
3Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER (CSIC/US/UPO/JA), Seville 41092, Spain
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  • ORCID record for Francisco-Javier Díaz-Corrales
Ozren Bogdanovic
4Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney 2010, New South Wales, Australia
5School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, 2052, Australia
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Paola Bovolenta
2Centro de Biología Molecular “Severo Ochoa,” (CSIC/UAM)
6CIBERER, ISCIII, Madrid 28049, Spain
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  • For correspondence: pbovolenta@cbm.csic.es jrmarmor@upo.es
Juan-Ramón Martínez-Morales
1Centro Andaluz de Biología del Desarrollo- CABD (CSIC/UPO/JA), Seville 41013, Spain
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  • ORCID record for Juan-Ramón Martínez-Morales
  • For correspondence: pbovolenta@cbm.csic.es jrmarmor@upo.es
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Summary

Sight depends on the tight cooperation between photoreceptors and pigmented cells. Both derive from common progenitors in which a single gene regulatory network (GRN) bifurcates into the neural retina (NR) and retinal-pigmented epithelium (RPE) programs. Although genetic studies have identified upstream nodes controlling these networks, their regulatory logic remains poorly investigated. Here, we characterize transcriptome dynamics (RNA-seq) and chromatin accessibility (ATAC-seq) in segregating NR/RPE populations in zebrafish. Analysis of active cis-regulatory modules and enriched transcription factor (TF) motives suggest extensive network redundancy and context-dependent TF activity. Downstream targets identification highlights an early recruitment of desmosomal genes in the flattening RPE, revealing Tead factors as upstream regulators. Investigation of GRNs dynamics uncovers an unexpected sequence of TF recruitment during RPE specification, which is conserved in humans. This systematic interrogation of the NR/RPE bifurcation should improve both genetic counselling for eye disorders and hiPSCs-to-RPE differentiation protocols for cell-replacement therapies in degenerative diseases.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 02, 2020.
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Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish
Lorena Buono, Silvia Naranjo, Tania Moreno-Marmol, Berta de la Cerda, Rocío Polvillo, Francisco-Javier Díaz-Corrales, Ozren Bogdanovic, Paola Bovolenta, Juan-Ramón Martínez-Morales
bioRxiv 2020.05.28.121038; doi: https://doi.org/10.1101/2020.05.28.121038
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Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish
Lorena Buono, Silvia Naranjo, Tania Moreno-Marmol, Berta de la Cerda, Rocío Polvillo, Francisco-Javier Díaz-Corrales, Ozren Bogdanovic, Paola Bovolenta, Juan-Ramón Martínez-Morales
bioRxiv 2020.05.28.121038; doi: https://doi.org/10.1101/2020.05.28.121038

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