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Updated: Jul 23, 2025

Studying Wnt Signaling During Patterning of Conducting Airways
Published on: October 16, 2016
Wnt/β-catenin signaling controls mouse eyelid growth by mediating epithelial-mesenchymal interactions
Xuming Zhu1, Makoto Senoo2, Sarah E Millar3
1Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Purpose:
To investigate the role of Wnt/β-catenin signaling in mouse eyelid development.
Methods:
Wnt/β-catenin signaling was disrupted by deleting supraorbital mesenchymal β-catenin or epithelial Wls. p63 was removed to determine whether the expression of Wnts is affected. The eyelid morphology was examined at different stages. Proliferation, apoptosis, and expression of Wnt ligands and their target genes were analyzed via immunofluorescence staining, TUNEL assay, and in situ hybridization.
Results:
Deletion of β-catenin in supraorbital mesenchyme abolishes eyelid growth by causing decreased proliferation in supraorbital epithelium and underlying mesenchyme. Inhibition of Wnt secretion by deleting Wls in supraorbital epithelium results in failure of eyelid development, similar to the effects of deleting mesenchymal β-catenin. Knockout of p63 results in formation of hypoplastic eyelids and reduced expression of several Wnt ligands in eyelid epithelium.
Conclusions:
Epithelial Wnt ligands activate mesenchymal Wnt/β-catenin signaling to control eyelid growth and their expression is partially regulated by p63.
Insights
Wnt/β-catenin signaling is crucial for mouse eyelid development. Disrupting this pathway, via Wnt ligands or β-catenin, halts eyelid growth and impacts proliferation.
Area of Science:
- Developmental biology
- Molecular signaling pathways
Background:
- Wnt/β-catenin signaling is a conserved pathway regulating cell proliferation, differentiation, and tissue patterning.
- Its precise role in mouse eyelid morphogenesis remains incompletely understood.
Purpose of the Study:
- To elucidate the function of Wnt/β-catenin signaling in mouse eyelid development.
- To investigate the interplay between epithelial Wnt ligands, mesenchymal Wnt/β-catenin activation, and p63 in eyelid formation.
Main Methods:
- Genetic manipulation of Wnt/β-catenin pathway components (β-catenin, Wls) in specific embryonic tissues.
- Conditional knockout of p63 to assess its regulatory role.
- Analysis of eyelid morphology, cell proliferation (immunofluorescence), apoptosis (TUNEL assay), and gene expression (in situ hybridization).
Main Results:
- Mesenchymal β-catenin deletion abrogated eyelid growth, reducing proliferation in adjacent epithelium and mesenchyme.
- Epithelial Wls deletion led to failed eyelid development, mirroring the effects of mesenchymal β-catenin loss.
- p63 knockout resulted in hypoplastic eyelids and diminished Wnt ligand expression in the epithelium.
Conclusions:
- Epithelial Wnt ligands are essential for activating mesenchymal Wnt/β-catenin signaling, which drives eyelid growth.
- p63 partially regulates the expression of these critical Wnt ligands.
- This study highlights a key signaling axis controlling mammalian eyelid development.
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