ROR2/PCP a New Pathway Controlling Endothelial Cell Polarity Under Flow Conditions

Area of Science:

• Cell Biology
• Vascular Biology
• Biophysics

Background:

• Endothelial cells (ECs) respond to blood flow forces, particularly laminar shear stress.
• EC polarization against flow is vital for vascular network development and remodeling.
• This study investigates the role of receptor tyrosine kinase-like orphan receptor 2 (ROR2) in EC responses to shear stress.

Purpose of the Study:

• To investigate the involvement of planar cell polarity via ROR2 in endothelial responses to laminar shear stress.
• To elucidate the molecular mechanisms by which ROR2 influences EC behavior under shear stress.

Main Methods:

• Generated a mouse model with EC-specific deletion of Ror2.
• Conducted in vitro loss- and gain-of-function experiments.
• Analyzed EC polarization, migration, and adherens junction dynamics.

Main Results:

• EC-specific Ror2 deletion impaired EC polarization during aortic development.
• ROR2 expression correlated with endothelial polarization levels.
• ROR2 relocalized to cell-cell junctions, forming complexes with VE-Cadherin and β-catenin, regulating adherens junctions.
• ROR2-induced polarity and junction remodeling depended on Cdc42 activation.

Conclusions:

• Identified the ROR2/planar cell polarity pathway as a novel mechanism controlling EC collective polarity under shear stress.
• ROR2 is essential for coordinating EC responses to laminar shear stress, impacting vascular development.