Epithelial-Mesenchymal Wnt Crosstalk Directs Planar Cell Polarity in the Developing Cochlea

Area of Science:

• Developmental Biology
• Genetics
• Cell Biology

Background:

• Cochlear hair cells are essential for hearing and rely on planar cell polarity (PCP) for proper orientation.
• The role of Wnt proteins in establishing cochlear PCP is not well understood.

Purpose of the Study:

• To investigate the function of Wnt proteins in cochlear development and planar cell polarity.
• To identify specific Wnts involved in hair cell orientation and cochlear outgrowth.

Main Methods:

• Inhibition of Wnt secretion using Wntless ablation in the cochlear epithelium.
• Computational cell-communication analysis to predict Wnt signaling pathways.
• Genetic deletion of specific Wnt genes (Wnt5a, Wnt7a, Wnt7b) in epithelial and mesenchymal compartments.

Main Results:

• Wntless ablation caused mild cochlear shortening and hair cell misorientation.
• Deletion of Wnt5a, Wnt7a, and Wnt7b additively shortened the cochlea but did not affect hair cell orientation.
• Combined ablation of epithelial and mesenchymal Wnts resulted in severe cochlear shortening and hair cell rotation defects, with loss of PCP proteins.

Conclusions:

• Wnt proteins act as crucial instructive cues for cochlear outgrowth and hair cell polarization.
• Distinct Wnts exhibit functional redundancy across epithelial and mesenchymal tissues, ensuring robust development.
• This study highlights a fail-safe mechanism in Wnt signaling for auditory development.