Collective polarization model for gradient sensing via Dachsous-Fat intercellular signaling

Area of Science:

• Developmental Biology
• Cell Biology
• Systems Biology

Background:

• The Dachsous-Fat signaling pathway, involving the Hippo pathway, is a crucial regulator of cell proliferation and tissue growth in Drosophila development.
• Mammalian homologs of this pathway function as tumor suppressors, underscoring its universal role in growth regulation.
• The Fat/Hippo pathway integrates morphogen gradients to influence cell polarization and division orientation, linking tissue growth with patterning.

Purpose of the Study:

• To develop a quantitative model for systematically characterizing the Fat/Hippo pathway's complex phenotypes.
• To gain insight into the underlying molecular mechanisms governing tissue growth and patterning.
• To explore how intercellular interactions contribute to collective cell polarization and sensitivity to morphogen gradients.

Main Methods:

• A phenomenological modeling approach was employed, considering a class of simple models constrained by observational data.
• The study focused on modeling the collective polarization of Fat-Dachsous complexes.
• A simplified signal transduction map was constructed to generalize existing models.

Main Results:

• Two modes of local/cooperative interactions among Fat-Dachsous complexes were predicted.
• These interactions are essential for collective tissue polarization and enhanced sensitivity to weak morphogen gradients.
• The model demonstrates that collective polarization integrates both the level and gradient of input signals, successfully reproducing known phenotypes.

Conclusions:

• The developed model provides a systematic characterization of the Fat/Hippo pathway, offering insights into its growth regulatory functions.
• Intercellular interactions play a critical role in the collective polarization of tissues and their response to signaling gradients.
• The findings generalize the positional value model and highlight the importance of cell-cell communication in tissue development.