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.
Sood
Raman
R
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
English
Milton A
MA
Belele
Christiane L
CL
Jin
Hao
H
Bishop
Kevin
K
Haskins
Rebecca
R
McKinney
Mary Cathleen
MC
Chahal
Jagman
J
Weinstein
Brant M
BM
Wen
Zilong
Z
Liu
P Paul
PP
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