PUBLICATION
The role of jak2a in zebrafish hematopoiesis
- Authors
- Ma, A.C., Ward, A.C., Liang, R., and Leung, A.Y.
- ID
- ZDB-PUB-070625-7
- Date
- 2007
- Source
- Blood 110(6): 1824-1830 (Journal)
- Registered Authors
- Leung, Anskar
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Division
- Cell Lineage
- Embryo, Nonmammalian/physiology*
- Enzyme Activation
- Erythroid Precursor Cells/metabolism
- Gene Expression Profiling
- Gene Expression Regulation, Developmental*
- Glycoproteins/metabolism
- Hematopoiesis*
- Intercellular Signaling Peptides and Proteins/metabolism
- Janus Kinase 2/genetics
- Janus Kinase 2/physiology*
- Neovascularization, Physiologic
- Oligonucleotide Array Sequence Analysis
- Phosphorylation
- STAT5 Transcription Factor/metabolism
- Signal Transduction
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 17545503 Full text @ Blood
Citation
Ma, A.C., Ward, A.C., Liang, R., and Leung, A.Y. (2007) The role of jak2a in zebrafish hematopoiesis. Blood. 110(6):1824-1830.
Abstract
Janus kinase 2 (Jak2) transduces signals from hematopoietic cytokines and a gain-of-function mutation (Jak2(V617F)) is associated with myeloproliferative diseases particularly polycythemia vera. In this study, we examined the role of jak2a in zebrafish embryos in knock-down and over-expression studies using morpholinos (MOs) targeting the 5'untranslated region (UTR) (jak2a(UTR)-MO) and splice-site junction (jak2a(SS)-MO) of jak2a, a Jak inhibitor AG490 and a constitutive-active form of jak2a (jak2a(ca)). At 18 and 24 hours-post-fertilization (hpf), jak2a is expressed predominantly in the intermediate cell mass (ICM, site of primitive hematopoiesis) of wild-type and chordin morphant embryos (characterized by expansion of ICM). Both jak2a MOs and AG490 reduced gata1(+) (erythroid) cells in Tg(gata1:GFP) embryos, stat5 phosphorylation and gene expression associated with early progenitors (scl and lmo2), erythroid (gata1, alphahe1 and betahe1) and myeloid [spi1 (early) and mpo (late)] lineages. The chordin morphant is associated with increased stat5 phosphorylation and both jak2a MOs and treatment with AG490 significantly ameliorated ICM expansion and hematopoietic gene up-regulation in these embryos. Injection of plasmid encoding jak2a(ca) significantly increased erythropoiesis and expression of gata1, alphahe1 and betahe1, spi1, mpo and l-plastin. In conclusion, zebrafish jak2a is involved in primitive hematopoiesis under normal and deregulated conditions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping