MiR-142-3p is essential for hematopoiesis and affects cardiac cell fate in zebrafish

Takahiko Nishiyama, Ruri Kaneda, Tomohiko Ono, Shugo Tohyama, Hisayuki Hashimoto, Jin Endo, Hikaru Tsuruta, Shinsuke Yuasa, Masaki Ieda, Shinji Makino, Keiichi Fukuda

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)755-761
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume425
Issue number4
DOIs
Publication statusPublished - 2012 Sep 7

Keywords

  • Cardiac development
  • Hematopoiesis
  • Mesoderm
  • MicroRNA
  • Rock2a

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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