Cluster Assembly Dynamics Drive Fidelity of Planar Cell Polarity Polarization

Area of Science:

• Cell biology
• Developmental biology
• Biophysics

Background:

• Planar cell polarity (PCP) signaling establishes cell asymmetry crucial for tissue development.
• PCP signaling relies on molecular subcomplexes forming asymmetric clusters at cell junctions.
• The mechanism driving the development of asymmetry within PCP clusters is not fully understood.

Purpose of the Study:

• To investigate the molecular dynamics of PCP cluster assembly and polarization.
• To determine the relationship between cluster size, asymmetry, and orientation.
• To elucidate how noisy cellular inputs are converted into robust tissue-level polarity.

Main Methods:

• Developed a novel method to quantify core PCP protein monomers within individual clusters in live animals.
• Performed spatiotemporal measurements in wild-type and mutant organisms.
• Utilized mathematical modeling to analyze cluster dynamics and infer molecular mechanisms.

Main Results:

• Demonstrated that PCP cluster assembly is a prerequisite for cell polarization.
• Showed that clusters become progressively more asymmetric and correctly oriented as they grow in size.
• Provided quantitative evidence linking cluster dynamics to the amplification of weak signaling inputs.

Conclusions:

• PCP cluster assembly dynamics are essential for establishing cell and tissue polarity.
• Cluster size acts as a critical factor in achieving robust and oriented PCP.
• The proposed model suggests a mechanism for converting noisy molecular signals into deterministic cellular outputs.