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A self-regulatory system of interlinked signaling feedback loops controls mouse limb patterning

Bénazet, Jean-Denis and Bischofberger, Mirko and Tiecke, Eva and Gonçalves, Alexandre and Martin, James F. and Zuniga, Aimée and Naef, Felix and Zeller, Rolf. (2009) A self-regulatory system of interlinked signaling feedback loops controls mouse limb patterning. Science, Vol. 323. pp. 1050-1053.

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Official URL: http://edoc.unibas.ch/dok/A6004357

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Anatomy > Developmental Genetics (Zeller/Zuniga)
UniBasel Contributors:Zeller, Rolf
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Association for the Advancement of Science
ISSN:0036-8075
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2013 11:14
Deposited On:01 Mar 2013 11:11

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