How does Wnt11 regulate the planar cell polarity? - with an updated view of extracellular distribution / diffusion of Wnt ligands

Planar cell polarity (PCP) is a kind of directional information of cells. Recent studies show that a family of secreted signaling proteins Wnt can direct the PCP.  However, it is still controversial how Wnt regulates the PCP, largely due to the lack of visualization of Wnt proteins.  Here we examined spatial distribution of Wnt11 in Xenopus gastrula by generating antibodies.  Interestingly, most of endogenous Wnt11 protein was arranged in a “parallel pattern” along the medio-lateral axis in the dorsal marginal zone.  This pattern is similar to polarized localization of GFP-Pk3 co-expressed with Vangl2, which is a recently reported method to visualize PCP.  Using this method, we observed that Wnt11 locally regulates core PCP components such as Pk3 and Frizzled7 in a short range (a few cell diameters).  Indeed, a membrane-tethered form of Wnt11 can direct PCP within a short range.  However, secreted wild-type Wnt11 can direct PCP over a long range (15-20 cell diameters), suggesting diffusion of the Wnt protein is essential for the long range, global coordination of PCP.  Importantly we found that Wnt11-EGFP colocalized with mRuby2-Pk3 in a highly polarized region, suggesting that some extracellular scaffolds for Wnt11 are formed in association with Pk3.  Thus, we propose that local and mutual regulation of Wnt11 and core PCP components could coordinate the cell polarity in a long range, through a relay-like effect and relocation of Wnt11 protein.

In addition, I will talk about extracellular distribution/diffusion of Wnt ligands, based on quantitative analyses including fluorescence correlation spectroscopy (FCS) and fluorescence decay after photoconversion (FDAP).

 

References

Yusuke Mii, Takayoshi Yamamoto, Ritsuko Takada, Shuji Mizumoto, Makoto Matsuyama, Shuhei Yamada, Shinji Takada, Masanori Taira

Nat. Commun. 8 (1) Dec 2017

 

Ritsuko Takada, Yusuke Mii, Elena Krayukhina, Yuusuke Maruyama, Kazuhiro Mio, Yoshikazu Sasaki, Takao Shinkawa, Chan-Gi Pack, Yasushi Sako, Chikara Sato, Susumu Uchiyama & Shinji Takada

Commun. Biol. 1(165) Oct 2018