PUBLICATION

Hedgehog Signaling Is Required for Adult Blood Stem Cell Formation in Zebrafish Embryos

Authors
Gering, M., and Patient, R.
ID
ZDB-PUB-050303-2
Date
2005
Source
Developmental Cell   8(3): 389-400 (Journal)
Registered Authors
Gering, Martin, Patient, Roger K.
Keywords
none
MeSH Terms
  • Veratrum Alkaloids/toxicity
  • Membrane Proteins/metabolism
  • Mutation/genetics
  • Cell Movement/drug effects
  • Cell Movement/physiology
  • Hematopoiesis/drug effects
  • Hematopoiesis/physiology*
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • T-Lymphocytes/cytology*
  • T-Lymphocytes/metabolism
  • Signal Transduction/drug effects
  • Signal Transduction/physiology*
  • Vascular Endothelial Growth Factor A/metabolism
  • DNA-Binding Proteins/metabolism
  • Neovascularization, Physiologic/drug effects
  • Neovascularization, Physiologic/physiology
  • Animals
  • Body Patterning/drug effects
  • Body Patterning/physiology
  • Hedgehog Proteins
  • Receptors, Notch
  • Zebrafish
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Developmental/physiology
  • Proto-Oncogene Proteins/metabolism
  • Transcription Factors/metabolism
  • Trans-Activators/genetics
  • Trans-Activators/metabolism*
  • Hematopoietic Stem Cells/cytology*
  • Hematopoietic Stem Cells/metabolism
  • Core Binding Factor Alpha 2 Subunit
PubMed
15737934 Full text @ Dev. Cell
Abstract
Studies with embryonic explants and embryonic stem cells have suggested a role for Hedgehog (Hh) signaling in hematopoiesis. However, targeted deletion of Hh pathway components in the mouse has so far failed to provide in vivo evidence. Here we show that zebrafish embryos mutant in the Hh pathway or treated with the Hh signaling inhibitor cyclopamine display defects in adult hematopoietic stem cell (HSC) formation but not in primitive hematopoiesis. Hh is required in the trunk at three consecutive stages during vascular development: for the medial migration of endothelial progenitors of the dorsal aorta (DA), for arterial gene expression, and for the formation of intersomitic vessel sprouts. Interference with Hh signaling during the first two stages also interferes with HSC formation. Furthermore, HSC and DA formation also share Vegf and Notch requirements, which further distinguishes them from primitive hematopoiesis and underlines their close relationship during vertebrate development.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping