title: Ddx46 is required for multi-lineage differentiation of hematopoietic stem cells in zebrafish.
abstract: 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 T-cell acute lymphocytic leukemia 1 (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 h postfertilization. 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 multilineage differentiation of HSCs during development, through the regulation of specific gene expressions.
authors: Department of Biological Science, Graduate School of Science, Hiroshima University, Hiroshima, Japan.
authors: Ryo
authors: R
authors: Hirabayashi
authors: Shunya
authors: S
authors: Hozumi
authors: Shin-Ichi
authors: S
authors: Higashijima
authors: Yutaka
authors: Y
authors: Kikuchi
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004920:Erythropoiesis / Q000235:genetics; D050982:GATA1 Transcription Factor / Q000096:biosynthesis; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D038041:Lymphopoiesis / Q000235:genetics; D009154:Mutation; D038042:Myelopoiesis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012326:RNA Splicing / Q000235:genetics; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D015534:Trans-Activators / Q000096:biosynthesis; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D053487:DEAD-box RNA Helicases; D050982:GATA1 Transcription Factor; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D015534:Trans-Activators; D029961:Zebrafish Proteins; D000099232:Proto-Oncogene Protein Spi-1; C489367:tal1 protein, zebrafish; C587481:Ddx46 protein, zebrafish
references: Development. 2011 Mar;138(6):1017-31
references: 21343360
references: Nat Genet. 2011 Dec 27;44(1):9-10
references: 22200771
references: Nature. 2009 Feb 12;457(7231):887-91
references: 19129762
references: Int J Dev Biol. 2010;54(6-7):1127-37
references: 20711990
references: Cell. 2008 Feb 22;132(4):631-44
references: 18295580
references: Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17304-8
references: 20823231
references: Exp Hematol. 2002 Dec;30(12):1381-9
references: 12482499
references: Blood. 2011 Jul 28;118(4):903-15
references: 21653321
references: Dev Dyn. 2012 May;241(5):879-89
references: 22411201
references: Nat Genet. 2011 Dec 11;44(1):53-7
references: 22158538
references: Dev Biol. 2002 Jun 15;246(2):274-95
references: 12051816
references: Blood. 2001 Aug 1;98(3):643-51
references: 11468162
references: Development. 1999 Sep;126(17):3735-45
references: 10433904
references: Dev Biol. 2003 Mar 1;255(1):48-61
references: 12618133
references: Dev Growth Differ. 2010 Feb;52(2):245-50
references: 20100247
references: Dev Biol. 1997 Feb 15;182(2):331-41
references: 9070331
references: Blood. 2011 Oct 13;118(15):4093-101
references: 21856868
references: Blood. 2010 Apr 8;115(14):2806-9
references: 20154212
references: Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21689-94
references: 19955420
references: EMBO J. 2011 Mar 16;30(6):1093-103
references: 21336259
references: Immunity. 2002 May;16(5):661-72
references: 12049718
references: Annu Rev Immunol. 2007;25:745-85
references: 17201678
references: Genetics. 2006 Oct;174(2):639-49
references: 16959904
references: Dev Biol. 1998 May 15;197(2):248-69
references: 9630750
references: Development. 2008 Aug;135(15):2521-9
references: 18579679
references: Nat Rev Mol Cell Biol. 2004 Mar;5(3):232-41
references: 14991003
references: PLoS One. 2012;7(3):e33675
references: 22442707
references: Mol Cell. 2007 Aug 3;27(3):339-52
references: 17679086
references: Dev Dyn. 1995 Jul;203(3):253-310
references: 8589427
references: Cell. 2009 Feb 20;136(4):701-18
references: 19239890
references: EMBO J. 1998 Jul 15;17(14):4029-45
references: 9670018
references: Dev Dyn. 2001 Dec;222(4):694-8
references: 11748838
references: Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10713-7
references: 7479870
references: Nature. 2011 Sep 11;478(7367):64-9
references: 21909114
references: Genes Cells. 2006 Aug;11(8):859-70
references: 16866870
references: Oncogene. 2000 Jul 13;19(30):3335-42
references: 10918590
references: EMBO J. 2004 Jan 28;23(2):376-85
references: 14713954
references: Nature. 2009 Feb 12;457(7231):892-5
references: 19182774
references: Mech Dev. 2002 Oct;118(1-2):179-85
references: 12351184
references: Dev Biol. 2007 Jul 15;307(2):179-94
references: 17559829
references: Nature. 1997 Jul 24;388(6640):397-400
references: 9237760
references: Blood. 2008 Apr 1;111(7):3331-42
references: 18182572
references: Nat Genet. 2011 Dec 11;44(1):47-52
references: 22158541
references: Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5454-9
references: 11960002
references: Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12792-7
references: 15256591
references: Cell. 1991 May 17;65(4):677-89
references: 1709592