Planar polarization of Vangl2 in the vertebrate neural plate is controlled by Wnt and Myosin II signaling

Abstract

The vertebrate neural tube forms as a result of complex morphogenetic movements, which require the functions of several core planar cell polarity (PCP) proteins, including Vangl2 and Prickle. Despite the importance of these proteins for neurulation, their subcellular localization and the mode of action have remained largely unknown. Here we describe the anteroposterior planar cell polarity (AP-PCP) of the cells in the Xenopus neural plate. At the neural midline, the Vangl2 protein is enriched at anterior cell edges and that this localization is directed by Prickle, a Vangl2-interacting protein. Our further analysis is consistent with the model, in which Vangl2 AP-PCP is established in the neural plate as a consequence of Wnt-dependent phosphorylation. Additionally, we uncover feedback regulation of Vangl2 polarity by Myosin II, reiterating a role for mechanical forces in PCP. These observations indicate that both Wnt signaling and Myosin II activity regulate cell polarity and cell behaviors during vertebrate neurulation.

Planar cell polarity in development and disease

“…c | Core PCP components can be found asymmetrically enriched along AP junctions of cells undergoing convergent extension in vertebrates, with Prickle (PK) typically localizing to the anterior cell faces and Dishevelled (DVL) along the posterior cell faces 79–82 . In the context of convergent extension, localization of PCP components at AP junctions coincides with the localization of filamentous actin enrichments and phosphorylated non-muscle Myosin II, which comprises the contractile actomyosin machinery that shrinks AP junctions 81,99,101,102 ; there is evidence that PCP components are involved in regulating this contractility 108,109 .…”

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

“…Neuroepithelial progenitors have been shown to exhibit planar polarized distribution of PCP proteins during CE, with an axis of planar polarity that is orthogonal to the overall direction of convergence. Pk and Vangl localize together at the level of AJs on anterior membranes in the frog neural plate (Ossipova et al, 2015b). In the fish, in which maturation of the apical surface of neuroepithelial progenitors is delayed (Araya et al, 2016), Pk and Vangl2 localize asymmetrically to the anterior side of immature progenitors (Ciruna et al, 2006;Roszko et al, 2015) and are subsequently recruited to anterior AJs (Davey et al, 2016).…”

Spatial and temporal aspects of Wnt signaling and planar cell polarity during vertebrate embryonic development

“…Classical examples of PCP are cuticular hairs of the Drosophila wing or ommatidia of the eye (Adler, 2012; Simons and Mlodzik, 2008). More recently, the spectrum of known tissues with PCP has been expanded to include mammalian cochlea (Montcouquiol et al, 2003), limb mesenchyme (Gao et al, 2011), ascidian notochord (Jiang et al, 2005), vertebrate skin (Devenport and Fuchs, 2008), axial mesoderm and neuroectoderm (Devenport, 2014; Nishimura et al, 2012; Ossipova, 2015a; Tissir and Goffinet, 2013; Wang and Nathans, 2007). …”

“…Consistent with these findings, Celsr1, Daam1, ROCK and Dishevelled were found enriched at anteroposterior cell faces in the chick and mouse neuroectoderm (McGreevy et al, 2015; Nishimura et al, 2012). In Xenopus , both endogenous Vangl2 and exogenous Vangl2/Prickle complexes accumulate at the most anterior edge of cells at the neural midline (Ossipova, 2015a). Mammalian axial mesoderm tissues, i. e. mouse notochord and the posterior node, are also polarized along the anteroposterior axis (Antic et al, 2010; Borovina et al, 2010; Hashimoto et al, 2010; Song et al, 2010).…”

“…Prickle directly associates with Vangl2 (Bastock et al, 2003; Jenny et al, 2003), but its function in PCP is poorly understood. In Xenopus , overexpressed Vangl2 is not visibly polarized in the neural plate, but its polarity becomes readily apparent in the presence of exogenous Prickle, indicating that Prickle activity is limiting (Ossipova, 2015a). Moreover, polarized Prickle/Vangl2 complex formation appears to require the physical interaction of the two proteins, as suggested by loss of PCP for Vangl2 protein lacking Prickle-binding domain (unpublished observations).…”