Document Detail


Hedgehog signalling via a calcitonin receptor-like receptor can induce arterial differentiation independently of VEGF signalling in zebrafish.
MedLine Citation:
PMID:  22668851     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Multiple signalling 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 signalling 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 arterial-venous 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 haematopoietic stem cell (HSC) gene expression. Importantly, whilst VEGF was thought to be absolutely essential for arterial fates, we find that normal and ectopic arterial differentiation can occur without VEGF signalling 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 signalling during arteriovenous specification. Finally, our experiments establish a dual function of Hedgehog during induction of runx1(+) HSCs.
Authors:
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     Date:  2012-6-5
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, United Kingdom;
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