Development of multilineage adult hematopoiesis in the zebrafish with a runx1 truncation mutation.
Runx1 is required for the emergence of hematopoietic stem cells (HSCs) from hemogenic endothelium during embryogenesis. However, its role in the generation and maintenance of HSCs during adult hematopoiesis remains uncertain. Here, we present analysis of a zebrafish mutant line carrying a truncation mutation, W84X, in runx1. The runx1(W84X/W84X) embryos showed blockage in the initiation of definitive hematopoiesis, but some embryos were able to recover from a larval "bloodless" phase and develop to fertile adults with multilineage hematopoiesis. Using cd41-green fluorescent protein transgenic zebrafish and lineage tracing, we demonstrated that the runx1(W84X/W84X) embryos developed cd41(+) HSCs in the aorta-gonad-mesonephros region, which later migrated to the kidney, the site of adult hematopoiesis. Overall, our data suggest that in zebrafish adult HSCs can be formed without an intact runx1.
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Raman
R
Sood
Milton A
MA
English
Christiane L
CL
Belele
Hao
H
Jin
Kevin
K
Bishop
Rebecca
R
Haskins
Mary Cathleen
MC
McKinney
Jagman
J
Chahal
Brant M
BM
Weinstein
Zilong
Z
Wen
P Paul
PP
Liu
D000818:Animals; D030801:Animals, Genetically Modified; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D008650:Mesonephros / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009154:Mutation; D040201:Platelet Membrane Glycoprotein IIb / Q000096:biosynthesis; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D050676:Core Binding Factor Alpha 2 Subunit; D040201:Platelet Membrane Glycoprotein IIb; D029961:Zebrafish Proteins; C472526:runx1 protein, zebrafish