Coupling mathematical modeling with a novel human intestinal stem cell system to understand feedback regulation during planar cell polarity.

ABSTRACT: The Planar Cell Polarity (PCP) complex regulates many diverse phenotypes. While recent literature has elucidated key mechanisms underlying PCP, a mechanistic understanding of how these components function as a system to drive polarity is lacking. Here, we develop a comprehensive multicellular mathematical model centered around key PCP phosphorylation events, directly simulating the protein interactions that drive PCP. Our model confirms key PCP phenotypes, including robust single-junction asymmetry and multicellular polarity alignment in the absence of extrinsic signals. It predicts unique roles for the two known positive feedback mechanisms and predicts that VANGL-mediated DVL phosphorylation may be an underappreciated negative feedback mechanism. To test model predictions, we employ tran

SUBMITTER: Breau KA 

PROVIDER: S-EPMC12637701 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature