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Dev Cell. 2017 Mar 27;40(6):552-565.e5. doi: 10.1016/j.devcel.2017.02.021.

MicroRNAs Establish Uniform Traits during the Architecture of Vertebrate Embryos.

Author information

1
Section of Cardiology, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT 06511, USA.
2
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
3
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.
4
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.
5
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.
6
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.

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.

KEYWORDS:

cardiovascular development; endothelial cells; environmental stress; miR-139; miR-223; miR-24; phenotypic variability; robustness; target gene networks; zebrafish mutants

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