PUBLICATION

Distinct roles for Scl in erythroid specification and maturation in zebrafish

Authors
Juarez, M.A., Su, F., Chun, S., Kiel, M.J., and Lyons, S.E.
ID
ZDB-PUB-051012-14
Date
2005
Source
The Journal of biological chemistry   280(50): 41636-41644 (Journal)
Registered Authors
Lyons, Susan, Su, Fengyun
Keywords
none
MeSH Terms
  • Alternative Splicing
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Basic Helix-Loop-Helix Transcription Factors/physiology*
  • Cell Differentiation
  • Cell Lineage
  • DNA/chemistry
  • DNA-Binding Proteins
  • Electrophoresis, Agar Gel
  • Erythroid-Specific DNA-Binding Factors/metabolism
  • Gene Expression Regulation, Developmental*
  • Hematopoiesis
  • In Situ Hybridization
  • Models, Genetic
  • Mutation
  • Phenotype
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins/metabolism
  • Proto-Oncogene Proteins/physiology*
  • RNA/chemistry
  • RNA, Antisense/chemistry
  • RNA, Messenger/metabolism
  • RNA, Small Interfering/metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells
  • Transcription Factors
  • Zebrafish
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
PubMed
16210319 Full text @ J. Biol. Chem.
Abstract
The stem cell leukemia (SCL) transcription factor is essential for vertebrate hematopoiesis. Using the powerful zebrafish model for embryonic analysis, we compared the effects of either reducint or ablating Scl using morpholino-modified antisense RNAs. Ablation of Scl resulted in loss of primitive and definitive hematopoiesis, consistent with its essential role in these processes. Interestingly, in embryos with severely reduced Scl levels, erythroid progenitors expressing gata1 and embryonic globin developed. Erythroid maturation was deficient in these Scl hypmorphs, supporting that Scl was required both for the erythroid specification and maturation steps, with maturation requiring higher Scl levels than specification. While all hematopoietic functions were rescued by wild-type Scl mRNA, an Scl DNA binding mutant rescued primitive and definitive hematopoiesis, but did not rescue primitive erythroid maturation. Together, we show that there is a distinct Scl hypomorphic phenotype and demonstrate that distinct functions are required for Scl's roles in the specification and differentiation of primitive and definitive hematopoietic lineages. Our results reveal that Scl participates in multiple processes requiring different levels and functions. Further we identify an Scl hypomorphic phenotype distinct from the null state.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes