A Self-Regulatory System of Interlinked Signaling Feedback Loops Controls Mouse Limb Patterning
Copyright policy )A Self-Regulatory System of Interlinked Signaling Feedback Loops Controls Mouse Limb Patterning
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.
- École Polytechnique Fédérale de Lausanne EPFL Switzerland
- University of Lausanne Switzerland
- Texas A&M Health Science Center United States
- Texas A&M University United States
- SIB Swiss Institute of Bioinformatics Switzerland
Feedback, Physiological, Limb Buds, Bone Morphogenetic Protein 4, Toes, Models, Biological, Epithelium, Fibroblast Growth Factors, Mesoderm, Mice, Forelimb, Animals, Intercellular Signaling Peptides and Proteins, Hedgehog Proteins, Body Patterning, Signal Transduction
Feedback, Physiological, Limb Buds, Bone Morphogenetic Protein 4, Toes, Models, Biological, Epithelium, Fibroblast Growth Factors, Mesoderm, Mice, Forelimb, Animals, Intercellular Signaling Peptides and Proteins, Hedgehog Proteins, Body Patterning, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).178 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!