title: miR-142-3p is essential for hematopoiesis and affects cardiac cell fate in zebrafish.
abstract: MicroRNAs (miRNAs) play a pivotal role during embryonic development and are required for proper organogenesis, including hematopoiesis. Recent studies suggest that, in the early mesoderm, there is an interaction between the hematopoietic and cardiac lineages. However, whether miRNAs can affect other lineages remains unknown. Therefore, we investigated whether hematopoietic miR-142-3p modulated the mesoderm formation. We report that knockdown (KD) of miR-142-3p, a hematopoietic-specific miRNA, in zebrafish resulted in loss of hematopoiesis during embryonic development. Intriguingly, we observed abnormal cardiac phenotypes and insufficiency of somitegenesis in KD-morphants. In the early developmental stage, a tiny heart, contractile dysfunction in the ventricle, cardiac arrhythmia (e.g. a 2:1 ratio of atrial:ventricular beating), and bradycardia were consistently observed. Histological examination revealed severe hypoplasia of the ventricle and disrupted muscle alignment. To determine the mechanism, we performed DNA microarray analysis. The results revealed that the expression of several mesodermal genes essential for the formation of cardiac and somatic mesoderm, such as no tail, T-box gene 16, mesoderm posterior a, one eye pinhead, and rho-associated, coiled-coil containing protein kinase (Rock2a), were increased in miR-142-3p KD-morphants. The luciferase reporter assay revealed that miR-142-3p repressed luciferase activity on the Rock2a 3'-UTR. The findings of the present study indicate that miR-142-3p plays a critical role in hematopoiesis, cardiogenesis, and somitegenesis in the early stage of mesoderm formation via regulation of Rock2a.
authors.affiliation: Department of Cardiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Ruri
authors.initials: R
authors.lastname: Kaneda
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ono
authors.forename: Shugo
authors.initials: S
authors.lastname: Tohyama
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Jin
authors.initials: J
authors.lastname: Endo
authors.forename: Hikaru
authors.initials: H
authors.lastname: Tsuruta
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Yuasa
authors.forename: Masaki
authors.initials: M
authors.lastname: Ieda
authors.forename: Shinji
authors.initials: S
authors.lastname: Makino
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006321:Heart / Q000196:embryology* / Q000502:physiology; D006410:Hematopoiesis; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D038081:Organogenesis; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
chemical_list: C577490:MIRN142 microRNA, zebrafish; D035683:MicroRNAs; D008156:Luciferases