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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.

Original publication

DOI

10.1016/j.devcel.2005.01.010

Type

Journal article

Journal

Dev Cell

Publication Date

03/2005

Volume

8

Pages

389 - 400

Keywords

Animals, Body Patterning, Cell Movement, Core Binding Factor Alpha 2 Subunit, DNA-Binding Proteins, Embryo, Nonmammalian, Gene Expression Regulation, Developmental, Hedgehog Proteins, Hematopoiesis, Hematopoietic Stem Cells, Membrane Proteins, Mutation, Neovascularization, Physiologic, Proto-Oncogene Proteins, Receptors, Notch, Signal Transduction, T-Lymphocytes, Trans-Activators, Transcription Factors, Vascular Endothelial Growth Factor A, Veratrum Alkaloids, Zebrafish