title: MicroRNAs Establish Uniform Traits during the Architecture of Vertebrate Embryos.
abstract: Proper functioning of an organism requires cells and tissues to behave in uniform, well-organized ways. How this optimum of phenotypes is achieved during the development of vertebrates is unclear. Here, we carried out a multi-faceted and single-cell resolution screen of zebrafish embryonic blood vessels upon mutagenesis of single and multi-gene microRNA (miRNA) families. We found that embryos lacking particular miRNA-dependent signaling pathways develop a vascular trait similar to wild-type, but with a profound increase in phenotypic heterogeneity. Aberrant trait variance in miRNA mutant embryos uniquely sensitizes their vascular system to environmental perturbations. We discovered a previously unrecognized role for specific vertebrate miRNAs to protect tissue development against phenotypic variability. This discovery marks an important advance in our comprehension of how miRNAs function in the development of higher organisms.
authors.affiliation: Section of Cardiology, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Dionna M
authors.initials: DM
authors.lastname: Kasper
authors.affiliation: Section of Cardiology, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Albertomaria
authors.initials: A
authors.lastname: Moro
authors.affiliation: Section of Cardiology, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Ristori
authors.affiliation: Section of Cardiology, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Narayanan
authors.affiliation: Section of Cardiology, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Guillermina
authors.initials: G
authors.lastname: Hill-Teran
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fleming
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Moreno-Mateos
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Vejnar
authors.affiliation: Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Donghoon
authors.initials: D
authors.lastname: Lee
authors.affiliation: Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Mengting
authors.initials: M
authors.lastname: Gu
authors.affiliation: Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA; Department of Computer Science, Yale University, New Haven, CT 06520, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giraldez
authors.affiliation: Section of Cardiology, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT 06511, USA; Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: stefania.nicoli@yale.edu.
authors.forename: Stefania
authors.initials: S
authors.lastname: Nicoli
mesh_terms: D000818:Animals; D001158:Arteries / Q000196:embryology / Q000378:metabolism; D002452:Cell Count; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D053263:Gene Regulatory Networks; D016678:Genome; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006720:Homozygote; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis; D016296:Mutagenesis / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011554:Pseudopodia / Q000378:metabolism; D019655:Quantitative Trait, Heritable; D013312:Stress, Physiological; D014714:Vertebrates / Q000196:embryology* / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
chemical_list: D035683:MicroRNAs
keywords: cardiovascular development; endothelial cells; environmental stress; miR-139; miR-223; miR-24; phenotypic variability; robustness; target gene networks; zebrafish mutants