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Updated: Jun 25, 2026
08:06
A Microfluidics Approach for the Functional Investigation of Signaling Oscillations Governing Somitogenesis
Published on: March 19, 2021
A self-regulatory system of interlinked signaling feedback loops controls mouse limb patterning
Jean-Denis Bénazet1, Mirko Bischofberger, Eva Tiecke
1Developmental Genetics, Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland.
Science (New York, N.Y.)
|February 21, 2009
Summary
Sonic hedgehog (SHH) and fibroblast growth factor (FGF) signaling pathways regulate limb development. Bone morphogenetic protein 4 (BMP4) initiates signaling, which SHH then propagates through Gremlin1 (GREM1) to control digit formation.
Area of Science:
- Developmental biology
- Molecular genetics
- Systems biology
Background:
- Embryogenesis relies on complex signaling between spatially distinct centers.
- Limb development involves epithelial-mesenchymal (e-m) feedback loops, notably involving Sonic Hedgehog (SHH), Fibroblast Growth Factor (FGF), and Bone Morphogenetic Protein (BMP) signaling.
- The role of Gremlin1 (GREM1) in mediating these feedback loops is crucial but not fully elucidated.
Purpose of the Study:
- To elucidate the regulatory mechanisms of e-m feedback loops in limb development.
- To understand the interplay between BMP4, SHH, and GREM1 in controlling digit specification.
- To investigate how these signaling pathways form a self-regulatory network for robust limb development.
Main Methods:
- Utilized mouse molecular genetics to study gene regulation.
- Employed mathematical modeling to analyze signaling dynamics.
- Investigated differential transcriptional regulation of Grem1.
Main Results:
- BMP4 signaling initiates e-m feedback, which is subsequently propagated by SHH.
- A switch mechanism links a rapid BMP4/GREM1 module to a slower SHH/GREM1/FGF loop.
- This interconnected network ensures robust regulation of distal limb development, accommodating variability.
Conclusions:
- The study reveals a novel regulatory switch in limb development involving BMP4 and SHH.
- A self-regulatory signaling network ensures precise control over digit specification.
- Interconnectivity among signaling pathways provides resilience and adaptability in limb development.
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