PUBLICATION
Analysis of opo cis-regulatory landscape uncovers Vsx2 requirement in early eye morphogenesis
- Authors
- Gago-Rodrigues, I., Fernández-Miñán, A., Letelier, J., Naranjo, S., Tena, J.J., Gómez-Skarmeta, J.L., Martinez-Morales, J.R.
- ID
- ZDB-PUB-150513-12
- Date
- 2015
- Source
- Nature communications 6: 7054 (Journal)
- Registered Authors
- Gómez-Skarmeta, José Luis, Letelier, Joaquin, Martinez-Morales, Juan R., Naranjo, Silvia, Tena, Juan
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Enhancer Elements, Genetic
- Epigenesis, Genetic
- Eye/embryology*
- Eye Proteins/genetics
- Eye Proteins/metabolism*
- Gene Expression Regulation, Developmental/physiology
- Gene Knockdown Techniques
- Genomics
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism*
- Humans
- Phylogeny
- Protein Binding
- Protein Footprinting
- RNA Splicing
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Retinal Neurons
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 25963169 Full text @ Nat. Commun.
Citation
Gago-Rodrigues, I., Fernández-Miñán, A., Letelier, J., Naranjo, S., Tena, J.J., Gómez-Skarmeta, J.L., Martinez-Morales, J.R. (2015) Analysis of opo cis-regulatory landscape uncovers Vsx2 requirement in early eye morphogenesis. Nature communications. 6:7054.
Abstract
The self-organized morphogenesis of the vertebrate optic cup entails coupling the activation of the retinal gene regulatory network to the constriction-driven infolding of the retinal epithelium. Yet the genetic mechanisms underlying this coordination remain largely unexplored. Through phylogenetic footprinting and transgenesis in zebrafish, here we examine the cis-regulatory landscape of opo, an endocytosis regulator essential for eye morphogenesis. Among the different conserved enhancers identified, we isolate a single retina-specific element (H6_10137) and show that its activity depends on binding sites for the retinal determinant Vsx2. Gain- and loss-of-function experiments and ChIP analyses reveal that Vsx2 regulates opo expression through direct binding to this retinal enhancer. Furthermore, we show that vsx2 knockdown impairs the primary optic cup folding. These data support a model by which vsx2, operating through the effector gene opo, acts as a central transcriptional node that coordinates neural retina patterning and optic cup invagination in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping