ZFIN ID: ZDB-PUB-130605-3
Ddx46 Is Required for Multi-Lineage Differentiation of Hematopoietic Stem Cells in Zebrafish
Hirabayashi, R., Hozumi, S., Higashijima, S.I., and Kikuchi, Y.
Date: 2013
Source: Stem cells and development   22(18): 2532-42 (Journal)
Registered Authors: Higashijima, Shin-ichi, Kikuchi, Yutaka
Keywords: none
MeSH Terms:
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors/biosynthesis
  • Cell Differentiation/genetics
  • Cell Proliferation
  • DEAD-box RNA Helicases/biosynthesis
  • DEAD-box RNA Helicases/genetics
  • DEAD-box RNA Helicases/metabolism*
  • Down-Regulation
  • Erythropoiesis/genetics
  • GATA1 Transcription Factor/biosynthesis
  • Gene Expression Regulation, Developmental/genetics*
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism*
  • Lymphopoiesis/genetics
  • Mutation
  • Myelopoiesis/genetics*
  • Proto-Oncogene Proteins/biosynthesis
  • RNA Splicing/genetics
  • Trans-Activators/biosynthesis
  • Zebrafish/genetics
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 23635340 Full text @ Stem Cells Dev.

Balanced and precisely controlled processes between self-renewal and differentiation of hematopoietic stem cells (HSCs) into all blood lineages are critical for vertebrate definitive hematopoiesis. However, the molecular mechanisms underlying the maintenance and differentiation of HSCs have not been fully elucidated. Here, we show that zebrafish Ddx46, encoding a DEAD-box RNA helicase, is expressed in HSCs of the caudal hematopoietic tissue (CHT). The number of HSCs expressing the molecular markers cmyb or tal1 was markedly reduced in Ddx46 mutants. However, massive cell death of HSCs was not detected, and proliferation of HSCs was normal in the CHT of the mutants at 48 hours post-fertilization. We found that myelopoiesis occurred, but erythropoiesis and lymphopoiesis were suppressed, in Ddx46 mutants. Consistent with these results, the expression of spi1, encoding a regulator of myeloid development, was maintained, but the expression of gata1a, encoding a regulator of erythrocyte development, was downregulated in the mutants. Taken together, our results provide the first genetic evidence that zebrafish Ddx46 is required for the multi-lineage differentiation of HSCs during development, through the regulation of specific gene expressions.