Document Detail

Hedgehog signaling via a calcitonin receptor-like receptor can induce arterial differentiation independently of VEGF signaling in zebrafish.
MedLine Citation:
PMID:  22668851     Owner:  NLM     Status:  MEDLINE    
Multiple signaling pathways control the specification of endothelial cells (ECs) to become arteries or veins during vertebrate embryogenesis. Current models propose that a cascade of Hedgehog (Hh), vascular endothelial growth factor (VEGF), and Notch signaling acts instructively on ECs to control the choice between arterial or venous fate. Differences in the phenotypes induced by Hh, VEGF, or Notch inhibition suggest that not all of the effects of Hh on arteriovenous specification are mediated by VEGF. We establish that full derepression of the Hh pathway in ptc1;ptc2 mutants converts the posterior cardinal vein into a second arterial vessel that manifests intact arterial gene expression, intersegmental vessel sprouting, and HSC gene expression. Importantly, although VEGF was thought to be absolutely essential for arterial fates, we find that normal and ectopic arterial differentiation can occur without VEGF signaling in ptc1;ptc2 mutants. Furthermore, Hh is able to bypass VEGF to induce arterial differentiation in ECs via the calcitonin receptor-like receptor, thus revealing a surprising complexity in the interplay between Hh and VEGF signaling during arteriovenous specification. Finally, our experiments establish a dual function of Hh during induction of runx1(+) HSCs.
Robert N Wilkinson; Marco J Koudijs; Roger K Patient; Philip W Ingham; Stefan Schulte-Merker; Fredericus J M van Eeden
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-06-05
Journal Detail:
Title:  Blood     Volume:  120     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-13     Completed Date:  2012-09-26     Revised Date:  2013-12-05    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  477-88     Citation Subset:  AIM; IM    
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MeSH Terms
Animals, Genetically Modified
Arteries / embryology,  metabolism
Calcitonin Receptor-Like Protein / metabolism*
Core Binding Factor Alpha 2 Subunit / metabolism
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Hedgehog Proteins / metabolism*
Hematopoietic Stem Cells / cytology,  metabolism
Receptors, Cell Surface / genetics,  metabolism
Receptors, Notch / metabolism
Signal Transduction
Vascular Endothelial Growth Factor A / metabolism*
Zebrafish / embryology*,  genetics,  metabolism*
Zebrafish Proteins / metabolism*
Grant Support
082962//Wellcome Trust; 082962/Z/07/Z//Wellcome Trust; G0700091//Medical Research Council
Reg. No./Substance:
0/Calcitonin Receptor-Like Protein; 0/Core Binding Factor Alpha 2 Subunit; 0/Hedgehog Proteins; 0/Receptors, Cell Surface; 0/Receptors, Notch; 0/Shha protein, zebrafish; 0/Vascular Endothelial Growth Factor A; 0/Zebrafish Proteins; 0/patched receptors; 0/runx1 protein, zebrafish

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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