Frizzled 4 Regulates Arterial Network Organization Through Noncanonical Wnt/Planar Cell Polarity Signaling

摘要: Rationale: A growing body of evidence supports the hypothesis that Wnt/planar cell polarity (PCP) pathway regulates endothelial proliferation and angiogenesis, but components mediate this regulation remain elusive. Objective: We investigated involvement one receptors, Frizzled4 (Fzd4), in process because its role has been implicated retinal vascular development. Methods Results: found loss fzd4 function mice results a striking reduction impairment distal small artery network heart kidney. report decreases migration ability cells to form tubes. show deletion induces defects expression level stable acetylated tubulin Golgi organization during migration. Deletion favors Wnt noncanonical AP1-dependent signaling, indicating Fzd4 plays pivotal favoring PCP signaling. Our data further demonstrate is predominantly localized on top plasma membrane, where it preferentially Dvl3 relocalization promote activation α-tubulin recruitment In pathological mouse angiogenic model, impairs response leads formation disorganized arterial network. Conclusions: These suggest major receptor involved through Wnt/PCP pathway.