TY - JOUR T1 - Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish JF - bioRxiv DO - 10.1101/2020.05.28.121038 SP - 2020.05.28.121038 AU - Lorena Buono AU - Silvia Naranjo AU - Tania Moreno-Marmol AU - Berta de la Cerda AU - Rocío Polvillo AU - Francisco-Javier Díaz-Corrales AU - Ozren Bogdanovic AU - Paola Bovolenta AU - Juan-Ramón Martínez-Morales Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/05/30/2020.05.28.121038.abstract N2 - Sight depends on the tight cooperation between photoreceptors and pigmented cells, an ancestral tandem in metazoans. In vertebrates, both cell types derive from common progenitors in which a single gene regulatory network (GRN) bifurcates into the neural retina (NR) and retinal-pigmented epithelium (RPE) specification programs. Classical genetic studies have identified the main upstream nodes controlling these networks; however, their detailed architecture and cis-regulatory logic remain poorly investigated. Here, we have characterized transcriptome dynamics (RNA-seq) and chromatin accessibility (ATAC-seq) in segregating NR/RPE populations in zebrafish. Analysis of differentially 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 cells, revealing Tead factors as their upstream regulators. Dynamic investigation of GRNs uncovers an unexpected sequence of TF recruitment during RPE specification, which is conserved in humans. This systematic interrogation of the NR/RPE bifurcating networks should improve both counselling of congenital eye disorders and hiPSCs-to-RPE differentiation protocols for cell-replacement therapies applicable to retinal degenerative diseases. ER -