Zebrafish microRNA miR-210-5p inhibits primitive myelopoiesis by silencing and mRNAs downstream of transcription factor genes.

Zebrafish genes encode transcription factors that lie on the apex of the regulatory hierarchy in primitive myelopoiesis. However, little is known about the roles of microRNAs in regulated processes. Performing RNA-Seq deep sequencing analysis of the expression changes of microRNAs in knockdown embryos, we identified miR-210-5p as a regulator of zebrafish primitive myelopoiesis. Knocking down (generating morphants) significantly increased miR-210-5p expression, whereas overexpression greatly reduced its expression. Consistent with inhibited primitive myelopoiesis in the morphants, miR-210-5p overexpression repressed primitive myelopoiesis, indicated by reduced numbers of granulocytes and macrophages. Moreover, knocking out miR-210 partially rescued the defective primitive myelopoiesis in zebrafish -knockdown embryos. Furthermore, we show that the restrictive role of miR-210-5p in zebrafish primitive myelopoiesis is due to impaired differentiation of hemangioblast into myeloid progenitor cells. By comparing the set of genes with reduced expression levels in the morphants to the predicted target genes of miR-210-5p, we found that and , encoding a forkhead box transcription factor and a solute carrier family 3 protein, respectively, are two direct downstream targets of miR-210-5p that mediate its inhibitory roles in zebrafish primitive myelopoiesis. In summary, our results reveal that miR-210-5p has an important role in the genetic network controlling zebrafish primitive myelopoiesis.