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Adult Mouse Digit Amputation and Regeneration: A Simple Model to Investigate Mammalian Blastema Formation and Intramembranous Ossification
Published on: July 12, 2019
Epithelium-Derived Wnt Ligands Are Essential for Maintenance of Underlying Digit Bone
Makoto Takeo1, Christopher S Hale2, Mayumi Ito1
1The Ronald O. Perelman Department of Dermatology, School of Medicine, New York University, New York, New York, USA; The Department of Cell Biology, School of Medicine, New York University, New York, New York, USA.
Abstract:
Clinically, many nail disorders accompany bone deformities, but whether the two defects are causally related is under debate. To investigate the potential interactions between the two tissue types, we analyzed epithelial-specific β-catenin-deficient mice, in which nail differentiation is abrogated. These mice showed regression of not only the nail plate but also of the underlying digit bone. Characterization of these bone defects revealed active bone resorption, which is suppressed by Wnt activation in osteoblast and osteoclast precursors. Furthermore, we found that Wntless expression, essential for Wnt ligand secretion, was lacking in the β-catenin-deficient nail epithelium and that genetic deletion of Wntless (Wls) in the nail epithelium led to the lack of Wnt activation in osteoblast and osteoclast precursors and subsequently led to defective regression of the underlying digit bone. Together, these data show that epithelial Wnt ligands can ultimately regulate Wnt signaling in osteoblast and osteoclast precursors, known to regulate bone homeostasis. These results reveal a critical role for the nail epithelium on the digit bone during homeostatic regeneration and show that Wnt/β-catenin signaling is critical for this interaction.
Insights
Nail epithelium Wnt ligands regulate digit bone development. Loss of epithelial β-catenin causes nail and bone defects by disrupting Wnt signaling, crucial for bone homeostasis.
Area of Science:
- Developmental Biology
- Skeletal Biology
- Epithelial Biology
Background:
- Nail disorders often correlate with bone deformities, but a causal link remains debated.
- Understanding tissue interactions is key to deciphering developmental and homeostatic processes.
Purpose of the Study:
- To investigate the interaction between nail epithelium and underlying digit bone.
- To elucidate the role of Wnt/β-catenin signaling in this interaction.
Main Methods:
- Analysis of epithelial-specific β-catenin-deficient mice with abrogated nail differentiation.
- Characterization of bone defects, including bone resorption.
- Genetic deletion of Wntless (Wls) in nail epithelium.
- Assessment of Wnt signaling activation in osteoblast and osteoclast precursors.
Main Results:
- β-catenin-deficient mice exhibited nail plate and digit bone regression.
- Bone defects involved active bone resorption, suppressed by Wnt activation.
- Absence of Wntless in deficient nail epithelium led to impaired Wnt activation in bone precursors.
- Genetic Wls deletion in nail epithelium resulted in defective digit bone regression.
Conclusions:
- Epithelial Wnt ligands regulate Wnt signaling in bone precursors, impacting bone homeostasis.
- The nail epithelium plays a critical role in digit bone regeneration.
- Wnt/β-catenin signaling is essential for the nail-bone interaction during regeneration.
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