PUBLICATION

Distinct Functions for Different scl Isoforms in Zebrafish Primitive and Definitive Hematopoiesis

Authors
Qian, F., Zhen, F., Xu, J., Huang, M., Li, W., and Wen, Z.
ID
ZDB-PUB-070504-27
Date
2007
Source
PLoS Biology   5(5): e132 (Journal)
Registered Authors
Wen, Zilong
Keywords
Embryos, Hematopoiesis, Zebrafish, Protein expression, Hematopoietic stem cells, Red blood cells, Erythroblasts, Messenger RNA
MeSH Terms
  • Cloning, Molecular
  • Protein Isoforms/metabolism
  • Molecular Sequence Data
  • Proto-Oncogene Proteins/genetics
  • Proto-Oncogene Proteins/metabolism*
  • DNA Primers
  • Sequence Analysis, DNA
  • Base Sequence
  • Zebrafish/genetics*
  • Zebrafish/physiology
  • In Situ Hybridization
  • Gene Expression*
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/metabolism*
  • Immunohistochemistry
  • Sequence Alignment
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Hematopoiesis/physiology*
  • Blotting, Northern
  • Hematopoietic Stem Cells/cytology*
  • Hematopoietic Stem Cells/physiology
  • Animals
  • Cell Differentiation/physiology
(all 24)
PubMed
17472439 Full text @ PLoS Biol.
Abstract
The stem-cell leukemia (SCL, also known as TAL1) gene encodes a basic helix-loop-helix transcription factor that is essential for the initiation of primitive and definitive hematopoiesis, erythrocyte and megakarocyte differentiation, angiogenesis, and astrocyte development. Here we report that the zebrafish produces, through an alternative promoter site, a novel truncated scl (tal1) isoform, scl-beta, which manifests a temporal and spatial expression distinct from the previously described full-length scl-alpha. Functional analysis reveals that while scl-alpha and -beta are redundant for the initiation of primitive hematopoiesis, these two isoforms exert distinct functions in the regulation of primitive erythroid differentiation and definitive hematopoietic stem cell specification. We further demonstrate that differences in the protein expression levels of scl-alpha and -beta, by regulating their protein stability, are likely to give rise to their distinct functions. Our findings suggest that hematopoietic cells at different levels of hierarchy are likely governed by a gradient of the Scl protein established through temporal and spatial patterns of expression of the different isoforms.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
s5
    		Point Mutation
    tg234
      		Point Mutation
      1 - 2 of 2
      Show
      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      tal1MO7-tal1MRPHLNO
      tal1MO8-tal1MRPHLNO
      tal1MO9-tal1MRPHLNO
      1 - 3 of 3
      Show
      Fish
      Fish
      npas4ls5/s5
      trim33tg234/tg234
      WT
      WT + MO7-tal1
      WT + MO7-tal1 + MO8-tal1
      WT + MO8-tal1
      1 - 6 of 6
      Show
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      No data available
      Mapping
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      Citation
      Qian, F., Zhen, F., Xu, J., Huang, M., Li, W., and Wen, Z. (2007) Distinct Functions for Different scl Isoforms in Zebrafish Primitive and Definitive Hematopoiesis. PLoS Biology. 5(5):e132.