RT Journal Article
T1 Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish.
A1 Buono, Lorena
A1 Corbacho, Jorge
A1 Naranjo, Silvia
A1 Almuedo-Castillo, María
A1 Moreno-Marmol, Tania
A1 de la Cerda, Berta
A1 Sanabria-Reinoso, Estefanía
A1 Polvillo, Rocío
A1 Díaz-Corrales, Francisco-Javier
A1 Bogdanovic, Ozren
A1 Bovolenta, Paola
A1 Martínez-Morales, Juan-Ramón
AB 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.
YR 2021
FD 2021-06-23
LK http://hdl.handle.net/10668/18035
UL http://hdl.handle.net/10668/18035
LA en
DS RISalud
RD Apr 11, 2025