PT  - JOURNAL ARTICLE
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
TI  - Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish
AID  - 10.1101/2020.05.28.121038
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.28.121038
4099  - http://biorxiv.org/content/early/2020/07/02/2020.05.28.121038.short
4100  - http://biorxiv.org/content/early/2020/07/02/2020.05.28.121038.full
AB  - 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 StatementThe authors have declared no competing interest.