title: Zebrafish microRNA-126 determines hematopoietic cell fate through c-Myb.
abstract: Precise regulatory mechanisms are required to appropriately modulate the cellular levels of transcription factors controlling cell fate decisions during blood cell development. In this study, we show that miR-126 is a novel physiological regulator of the proto-oncogene c-myb during definitive hematopoiesis. We show that knockdown of miR-126 results in increased c-Myb levels and promotes erythropoiesis at the expense of thrombopoiesis in vivo. We further provide evidence that specification of thrombocyte versus erythrocyte cell lineages is altered by the concerted activities of the microRNAs (miRNAs) miR-126 and miR-150. Both miRNAs are required but not sufficient individually to precisely regulate the cell fate decision between erythroid and megakaryocytic lineages during definitive hematopoiesis in vivo. These results support the notion that miRNAs not only function to provide precision to developmental programs but also are essential determinants in the control of variable potential functions of a single gene during hematopoiesis.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. clemens.grabher@kit.edu
authors.forename: C
authors.initials: C
authors.lastname: Grabher
authors.forename: E M
authors.initials: EM
authors.lastname: Payne
authors.forename: A B
authors.initials: AB
authors.lastname: Johnston
authors.forename: N
authors.initials: N
authors.lastname: Bolli
authors.forename: E
authors.initials: E
authors.lastname: Lechman
authors.forename: J E
authors.initials: JE
authors.lastname: Dick
authors.forename: J P
authors.initials: JP
authors.lastname: Kanki
authors.forename: A T
authors.initials: AT
authors.lastname: Look
mesh_terms: D000818:Animals; D001483:Base Sequence; D019070:Cell Lineage; D004920:Erythropoiesis; D006410:Hematopoiesis; D035683:MicroRNAs / Q000502:physiology*; D008969:Molecular Sequence Data; D020598:Proto-Oncogene Proteins c-myb / Q000502:physiology*; D034061:Thrombopoiesis; D015027:Zebrafish / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C549766:Mirn126 microRNA, zebrafish; D020598:Proto-Oncogene Proteins c-myb