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.

The Ocular Surface
|July 15, 2023
PubMed
Abstract

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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