New mouse models for high resolution and live imaging of planar cell polarity proteins in vivo

Development. 2021 Sep 15;148(18):dev199695. doi: 10.1242/dev.199695. Epub 2021 Sep 23.

Abstract

The collective polarization of cellular structures and behaviors across a tissue plane is a near universal feature of epithelia known as planar cell polarity (PCP). This property is controlled by the core PCP pathway, which consists of highly conserved membrane-associated protein complexes that localize asymmetrically at cell junctions. Here, we introduce three new mouse models for investigating the localization and dynamics of transmembrane PCP proteins: Celsr1, Fz6 and Vangl2. Using the skin epidermis as a model, we characterize and verify the expression, localization and function of endogenously tagged Celsr1-3xGFP, Fz6-3xGFP and tdTomato-Vangl2 fusion proteins. Live imaging of Fz6-3xGFP in basal epidermal progenitors reveals that the polarity of the tissue is not fixed through time. Rather, asymmetry dynamically shifts during cell rearrangements and divisions, while global, average polarity of the tissue is preserved. We show using super-resolution STED imaging that Fz6-3xGFP and tdTomato-Vangl2 can be resolved, enabling us to observe their complex localization along junctions. We further explore PCP fusion protein localization in the trachea and neural tube, and discover new patterns of PCP expression and localization throughout the mouse embryo.

Keywords: Celsr1; Epidermis; Frizzled 6; Planar cell polarity; Super resolution; Vangl2.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Patterning / physiology
  • Cell Polarity / physiology*
  • Diagnostic Imaging / methods
  • Embryo, Mammalian / metabolism
  • Embryo, Mammalian / physiology
  • Epidermal Cells / metabolism
  • Epidermal Cells / physiology
  • Epidermis / metabolism
  • Epidermis / physiology
  • Epithelium / metabolism
  • Epithelium / physiology
  • Frizzled Receptors / metabolism
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Nerve Tissue Proteins / metabolism
  • Neural Tube / metabolism
  • Neural Tube / physiology
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / physiology
  • Trachea / metabolism
  • Trachea / physiology

Substances

  • Frizzled Receptors
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, G-Protein-Coupled