PUBLICATION
Regulation of endoderm formation and left-right asymmetry by miR-92 during early zebrafish development
- Authors
- Li, N., Wei, C., Olena, A.F., and Patton, J.G.
- ID
- ZDB-PUB-110429-21
- Date
- 2011
- Source
- Development (Cambridge, England) 138(9): 1817-1826 (Journal)
- Registered Authors
- Li, Nan, Patton, James G.
- Keywords
- Kupffer's vesicle, gata5, Left-right asymmetry, miR-92(mir92), zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Base Sequence
- Body Patterning/genetics*
- Cardia/embryology
- Cardia/metabolism
- Embryo, Nonmammalian
- Endoderm/embryology*
- Endoderm/metabolism
- GATA5 Transcription Factor/genetics
- GATA5 Transcription Factor/metabolism
- Gene Expression Regulation, Developmental
- MicroRNAs/genetics
- MicroRNAs/metabolism
- MicroRNAs/physiology*
- Tissue Distribution
- Viscera/embryology
- Viscera/metabolism
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 21447552 Full text @ Development
Citation
Li, N., Wei, C., Olena, A.F., and Patton, J.G. (2011) Regulation of endoderm formation and left-right asymmetry by miR-92 during early zebrafish development. Development (Cambridge, England). 138(9):1817-1826.
Abstract
microRNAs (miRNAs) are a family of 21-23 nucleotide endogenous non-coding RNAs that post-transcriptionally regulate gene expression in a sequence-specific manner. Typically, miRNAs downregulate target genes by recognizing and recruiting protein complexes to 3'UTRs, followed by translation repression or mRNA degradation. miR-92 is a well-studied oncogene in mammalian systems. Here, using zebrafish as a model system, we uncovered a novel tissue-inductive role for miR-92 during early vertebrate development. Overexpression resulted in reduced endoderm formation during gastrulation with consequent cardia and viscera bifida. By contrast, depletion of miR-92 increased endoderm formation, which led to abnormal Kupffer's vesicle development and left-right patterning defects. Using target prediction algorithms and reporter constructs, we show that gata5 is a target of miR-92. Alteration of gata5 levels reciprocally mirrored the effects of gain and loss of function of miR-92. Moreover, genetic epistasis experiments showed that miR-92-mediated defects could be substantially suppressed by modulating gata5 levels. We propose that miR-92 is a critical regulator of endoderm formation and left-right asymmetry during early zebrafish development and provide the first evidence for a regulatory function for gata5 in the formation of Kupffer's vesicle and left-right patterning.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping