PUBLICATION

Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish

Authors
Buono, L., Corbacho, J., Naranjo, S., Almuedo-Castillo, M., Moreno-Marmol, T., de la Cerda, B., Sanbria-Reinoso, E., Polvillo, R., Díaz-Corrales, F.J., Bogdanovic, O., Bovolenta, P., Martínez-Morales, J.R.
ID
ZDB-PUB-210625-3
Date
2021
Source
Nature communications   12: 3866 (Journal)
Registered Authors
Bogdanovic, Ozren, Bovolenta, Paola, Martinez-Morales, Juan R., Moreno-Mármol, Tania, Naranjo, Silvia
Keywords
none
Datasets
GEO:GSE150189, GEO:GSE150346
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Chromatin Immunoprecipitation Sequencing/methods
  • Cluster Analysis
  • Gene Expression Profiling/methods*
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks*
  • Humans
  • Induced Pluripotent Stem Cells/cytology
  • Induced Pluripotent Stem Cells/metabolism
  • Morphogenesis/genetics*
  • RNA-Seq/methods
  • Retinal Pigment Epithelium/cytology
  • Retinal Pigment Epithelium/embryology
  • Retinal Pigment Epithelium/metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors/classification
  • Transcription Factors/genetics
  • Zebrafish/embryology
  • Zebrafish/genetics*
PubMed
34162866 Full text @ Nat. Commun.
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.
Errata / Notes
This article is corrected by ZDB-PUB-210730-2 .
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping