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Updated: Jan 6, 2026
06:49
Analysis of Cell Differentiation, Morphogenesis, and Patterning During Chicken Embryogenesis Using the Soaked-Bead Assay
Published on: January 12, 2022
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Dual Bmp-negative feedback loops modulate function of both AER and ZPA to buffer and constrain postaxial digit number
1Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Summary
Sonic hedgehog (Shh) signaling controls limb development by regulating Bone morphogenetic proteins (Bmps). These Bmps act as relay signals to limit the limb bud
Area of Science:
- Developmental biology
- Evolutionary biology
- Genetics
Background:
- Tetrapod digit number is typically five (pentadactyly).
- Digit patterning involves Sonic hedgehog (Shh) from the Zone of Polarizing Activity (ZPA) and FGF from the Apical Ectodermal Ridge (AER).
- The precise mechanism balancing Shh signaling to maintain pentadactyly is unclear.
Purpose of the Study:
- To investigate how Shh signaling modulates AER function in tetrapod limb development.
- To elucidate the role of Bone morphogenetic proteins (Bmps) in mediating Shh effects.
- To understand the feedback mechanisms regulating digit number.
Main Methods:
- Genetic manipulation in mouse models.
- Analysis of gene expression patterns.
- Functional studies of signaling pathways.
Main Results:
- Shh signaling influences AER function indirectly through Bmp relay signals, not direct action.
- Shh-induced Bmps negatively feedback on the ZPA, down-regulating Shh expression.
- Dual Bmp-driven negative feedback loops maintain balanced Bmp levels and constrain digit number.
Conclusions:
- Bmp-mediated feedback loops are crucial for regulating Shh signaling.
- These mechanisms robustly balance limb development to ensure pentadactyly.
- The findings clarify a key aspect of vertebrate limb patterning.
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