title: Regulation of endoderm formation and left-right asymmetry by miR-92 during early zebrafish development.
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.
authors: Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA.
authors: Nan
authors: N
authors: Li
authors: Chunyao
authors: C
authors: Wei
authors: Abigail F
authors: AF
authors: Olena
authors: James G
authors: JG
authors: Patton
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics*; D002299:Cardia / Q000196:embryology / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004707:Endoderm / Q000196:embryology* / Q000378:metabolism; D050992:GATA5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014018:Tissue Distribution; D014781:Viscera / Q000196:embryology / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
chemical_list: D050992:GATA5 Transcription Factor; D035683:MicroRNAs