Polycystin signaling is required for directed endothelial cell migration and lymphatic development

Area of Science:

• Developmental biology
• Genetics
• Vascular biology

Background:

• Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited kidney disorder.
• Mutations in PKD1 or PKD2 genes cause ADPKD.
• Mice lacking Pkd1 or Pkd2 die during embryonic development with severe edema and vascular abnormalities.

Purpose of the Study:

• To investigate the underlying cause of embryonic edema and vascular defects in Pkd1- and Pkd2-null mice.
• To determine the role of polycystin signaling in lymphatic development and endothelial cell function.

Main Methods:

• Analysis of Pkd1- and Pkd2-null mouse embryos.
• Assessment of lymphatic vessel density and branching.
• Cell-based assays to evaluate endothelial cell migration and polarity.

Main Results:

• Pkd1 and Pkd2 mutant embryos showed reduced lymphatic vessel density and aberrant vascular branching.
• Defects in the migration of early lymphatic endothelial cell precursors were observed.
• Endothelial cells with depleted PKD1 or PKD2 exhibited impaired directional migration and failed to establish front-rear polarity.

Conclusions:

• Embryonic edema in Pkd1- and Pkd2-null mice is linked to defects in lymphatic development.
• Polycystin signaling plays a critical role in lymphatic development and endothelial cell migration.
• These findings reveal a novel function for polycystins in vascular development.