A self-regulatory system of interlinked signaling feedback loops controls mouse limb patterning
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 1194128
Author(s) Bénazet, Jean-Denis; Bischofberger, Mirko; Tiecke, Eva; Gonçalves, Alexandre; Martin, James F; Zuniga, Aimée; Naef, Felix; Zeller, Rolf
Author(s) at UniBasel Zeller, Rolf
Year 2009
Title A self-regulatory system of interlinked signaling feedback loops controls mouse limb patterning
Journal Science
Volume 323
Number 5917
Pages / Article-Number 1050-3
Abstract Embryogenesis depends on self-regulatory interactions between spatially separated signaling centers, but few of these are well understood. Limb development is regulated by epithelial-mesenchymal (e-m) feedback loops between sonic hedgehog (SHH) and fibroblast growth factor (FGF) signaling involving the bone morphogenetic protein (BMP) antagonist Gremlin1 (GREM1). By combining mouse molecular genetics with mathematical modeling, we showed that BMP4 first initiates and SHH then propagates e-m feedback signaling through differential transcriptional regulation of Grem1 to control digit specification. This switch occurs by linking a fast BMP4/GREM1 module to the slower SHH/GREM1/FGF e-m feedback loop. This self-regulatory signaling network results in robust regulation of distal limb development that is able to compensate for variations by interconnectivity among the three signaling pathways.
Publisher American Association for the Advancement of Science
ISSN/ISBN 0036-8075
edoc-URL http://edoc.unibas.ch/dok/A6004357
Full Text on edoc No
Digital Object Identifier DOI 10.1126/science.1168755
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/19229034
ISI-Number WOS:000263478400039
Document type (ISI) Journal Article
 
   

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