ZFIN ID: ZDB-PUB-050303-2
Hedgehog Signaling Is Required for Adult Blood Stem Cell Formation in Zebrafish Embryos
Gering, M., and Patient, R.
Date: 2005
Source: Developmental Cell   8(3): 389-400 (Journal)
Registered Authors: Gering, Martin, Patient, Roger K.
Keywords: none
MeSH Terms:
  • Animals
  • Body Patterning/drug effects
  • Body Patterning/physiology
  • Cell Movement/drug effects
  • Cell Movement/physiology
  • Core Binding Factor Alpha 2 Subunit
  • DNA-Binding Proteins/metabolism
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Developmental/physiology
  • Hedgehog Proteins
  • Hematopoiesis/drug effects
  • Hematopoiesis/physiology*
  • Hematopoietic Stem Cells/cytology*
  • Hematopoietic Stem Cells/metabolism
  • Membrane Proteins/metabolism
  • Mutation/genetics
  • Neovascularization, Physiologic/drug effects
  • Neovascularization, Physiologic/physiology
  • Proto-Oncogene Proteins/metabolism
  • Receptors, Notch
  • Signal Transduction/drug effects
  • Signal Transduction/physiology*
  • T-Lymphocytes/cytology*
  • T-Lymphocytes/metabolism
  • Trans-Activators/genetics
  • Trans-Activators/metabolism*
  • Transcription Factors/metabolism
  • Vascular Endothelial Growth Factor A/metabolism
  • Veratrum Alkaloids/toxicity
  • Zebrafish
PubMed: 15737934 Full text @ Dev. Cell
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.