PUBLICATION
Zebrafish mll is essential for haematopoiesis
- Authors
- Wan, X., Hu, B., Liu, J.X., Feng, X., and Xiao, W.
- ID
- ZDB-PUB-110803-6
- Date
- 2011
- Source
- The Journal of biological chemistry 286(38): 33345-57 (Journal)
- Registered Authors
- Feng, Xi, Hu, Bo, Liu, Jing-xia, Wan, Xiaoyang, Xiao, Wuhan
- Keywords
- development, gene regulation, hematopoiesis, leukemia, zebrafish, gadd45aa, hox, mll
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Biomarkers/metabolism
- Blood Circulation/drug effects
- Conserved Sequence/genetics
- Embryonic Development/drug effects
- Embryonic Development/genetics
- Evolution, Molecular
- Gene Expression Regulation, Developmental/drug effects
- Gene Knockdown Techniques
- Hematopoiesis/drug effects
- Hematopoiesis/genetics*
- Hematopoietic Stem Cells/cytology
- Hematopoietic Stem Cells/drug effects
- Hematopoietic Stem Cells/metabolism
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism
- Intracellular Signaling Peptides and Proteins/metabolism
- Molecular Sequence Data
- Morphogenesis/drug effects
- Morphogenesis/genetics
- Myeloid-Lymphoid Leukemia Protein/chemistry
- Myeloid-Lymphoid Leukemia Protein/genetics*
- Myeloid-Lymphoid Leukemia Protein/metabolism
- Oligonucleotides, Antisense/pharmacology
- Peptides/metabolism
- Zebrafish/genetics*
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 21784840 Full text @ J. Biol. Chem.
Citation
Wan, X., Hu, B., Liu, J.X., Feng, X., and Xiao, W. (2011) Zebrafish mll is essential for haematopoiesis. The Journal of biological chemistry. 286(38):33345-57.
Abstract
Studies implicate an important role for the mixed lineage leukemia (Mll) gene in haematopoiesis, mainly through maintaining Hox gene expression. However, the mechanisms underlying Mll-mediated haematopoiesis during embryogenesis remain largely unclear. Here, we investigate the role of mll during zebrafish embryogenesis, in particular, haematopoiesis. Mll depletion caused severe defects in haematopoiesis as indicated by a lack of blood flow and mature blood cells as well as a significant reduction in expression of hematopoietic progenitor and mature blood cell markers. Furthermore, mll depletion prevented the differentiation of hematopoietic progenitors. In addition, we identified the N-terminal mini-peptide of Mll acted as a dominant negative form to disrupt normal function of mll during embryogenesis. As expected, mll knockdown altered the expression of a subset of hox genes. However, overexpression of these down-regulated hox genes only partially rescued the blood deficiency, suggesting that mll may target additional genes to regulate haematopoiesis. In the mll morphants, microarray analysis revealed a dramatic up-regulation of gadd45αa. Multiple assays indicate that mll inhibited gadd45αa expression and that overexpression of gadd45αa mRNA led to a phenotype similar to the one seen in the mll morphants. Taken together, these findings demonstrate that zebrafish mll plays essential roles in haematopoiesis and that gadd45αa may serve as a potential down-stream target for mediating mll function in haematopoiesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping