Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish

Lorena Buono, Jorge Corbacho, Silvia Naranjo, María Almuedo-Castillo, Tania Moreno-Marmol, Berta Cerda, Estefanía Sanabria-Reinoso, Rocío Polvillo, Francisco-Javier Díaz-Corrales, Ozren Bogdanovic, Paola Bovolenta () and Juan-Ramón Martínez-Morales ()
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Lorena Buono: Centro Andaluz de Biología del Desarrollo-CABD (CSIC/UPO/JA)
Jorge Corbacho: Centro Andaluz de Biología del Desarrollo-CABD (CSIC/UPO/JA)
Silvia Naranjo: Centro Andaluz de Biología del Desarrollo-CABD (CSIC/UPO/JA)
María Almuedo-Castillo: Centro Andaluz de Biología del Desarrollo-CABD (CSIC/UPO/JA)
Tania Moreno-Marmol: Centro de Biología Molecular Severo Ochoa (CSIC/UAM)
Berta Cerda: Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER (CSIC/US/UPO/JA)
Estefanía Sanabria-Reinoso: Centro Andaluz de Biología del Desarrollo-CABD (CSIC/UPO/JA)
Rocío Polvillo: Centro Andaluz de Biología del Desarrollo-CABD (CSIC/UPO/JA)
Francisco-Javier Díaz-Corrales: Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER (CSIC/US/UPO/JA)
Ozren Bogdanovic: Garvan Institute of Medical Research
Paola Bovolenta: Centro de Biología Molecular Severo Ochoa (CSIC/UAM)
Juan-Ramón Martínez-Morales: Centro Andaluz de Biología del Desarrollo-CABD (CSIC/UPO/JA)

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Sight depends on the tight cooperation between photoreceptors and pigmented cells, which derive from common progenitors through the bifurcation of a single gene regulatory network 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 and chromatin accessibility in segregating NR/RPE populations in zebrafish. We analyze cis-regulatory modules and enriched transcription factor motives to show extensive network redundancy and context-dependent activity. We identify downstream targets, highlighting an early recruitment of desmosomal genes in the flattening RPE and revealing Tead factors as upstream regulators. We investigate the RPE specification network dynamics to uncover an unexpected sequence of transcription factors recruitment, which is conserved in humans. This systematic interrogation of the NR/RPE bifurcation should improve both genetic counseling for eye disorders and hiPSCs-to-RPE differentiation protocols for cell-replacement therapies in degenerative diseases.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24169-7

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DOI: 10.1038/s41467-021-24169-7

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