The PCP Pathway Instructs the Planar Orientation of Ciliated Cells in the Xenopus Larval Skin

Abstract

Planar cell polarity (PCP) is a property of epithelial tissues where cellular structures coordinately orient along a two-dimensional plane lying orthogonal to the axis of apical-basal polarity. PCP is particularly striking in tissues where multiciliate cells generate a directed fluid flow, as seen, for example, in the ciliated epithelia lining the respiratory airways or the ventricles of the brain. To produce directed flow, ciliated cells orient along a common planar axis in a direction set by tissue patterning, but how this is achieved in any ciliated epithelium is unknown. Here, we show that the planar orientation of Xenopus multiciliate cells is disrupted when components in the PCP-signaling pathway are altered non-cell-autonomously. We also show that wild-type ciliated cells located at a mutant clone border reorient toward cells with low Vangl2 or high Frizzled activity and away from those with high Vangl2 activity. These results indicate that the PCP pathway provides directional non-cell-autonomous cues to orient ciliated cells as they differentiate, thus playing a critical role in establishing directed ciliary flow.

The Rac1 regulator ELMO controls basal body migration and docking in multiciliated cells through interaction with Ezrin

“…Since there are monociliated and multiciliated pronephric tubule cells (Liu et al, 2007), one possible explanation is that monociliated cells are less affected by defective ELMO/Ezrin signalling and therefore still form a cilium. Consistent with this possibility, Xenopus vangl2 morphants are characterised by a reduced number of cilia in skin cells (Mitchell et al, 2009), whereas cilia in the gastrocoel roof plate are reportedly unaffected (Antic et al, 2010;Werner and Mitchell, 2012). In the same way, gastrocoel roof plate cilia are significantly shorter but not missing in nubp1 morphants (Ioannou et al, 2013).…”

Planar cell polarity in moving cells: think globally, act locally

“…1B-D) (Butler and Wallingford, 2015;Chu and Sokol, 2016;Ciruna et al, 2006;Davey et al, 2016;Deans et al, 2007;Devenport et al, 2011;Hashimoto et al, 2010;Vladar et al, 2012;Yin et al, 2008). Altering the expression of Vang or Fz homologs mosaically in the frog skin or in the sensory epithelium of the chick ear disrupts the polarity of adjacent wild-type cells, suggesting that the molecular interactions between core PCP components that amplify and maintain their asymmetric localization are conserved between fly and vertebrate epithelia (Mitchell et al, 2009;Sienknecht et al, 2011). As we discuss later, this paired cell-autonomous and noncell-autonomous function is a deeply conserved characteristic of the pathway even in migrating cells.…”

Planar polarity of multiciliated ependymal cells involves the anterior migration of basal bodies regulated by non-muscle myosin II

“…To generate directional fluid flow over the surface of a tissue, ciliary beating must be coordinated in the same direction. Recent studies have shown that the planar cell polarity (PCP) pathway, a downstream branch of Wnt signaling, plays important roles in directing the ciliary beating of multiciliated cells in Xenopus larval skin and mouse ependymal cells (Ganner et al, 2009;Guirao et al, 2010;Mitchell et al, 2007;Mitchell et al, 2009;Park et al, 2008;Tissir et al, 2010). In addition, fluid flowmediated mechanisms and functional ciliary axonemes are involved in establishing the planar polarity of ciliary orientation (Guirao et al, 2010;Mitchell et al, 2007).…”