Reactome | PCP/CE pathway

PCP/CE pathway

Stable Identifier

R-HSA-4086400

Type

Pathway

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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The planar cell polarity (PCP) pathway controls the establishment of polarity within the plane of a sheet of cells. PCP was initially characterized in Drosophila, where it controls the arrangement of hair bristles and photoreceptors in the eye (reviewed in Maung and Jenny, 2011). In vertebrates, PCP regulates convergent extension (CE, a process by which a tissue narrows along one axis and lengthens along a perpendicular one), closure of the neural tube, hair orientation and inner ear development, among others (reviewed in Seifert and Mlodzik, 2007). Studies in Drosophila identified a core group of PCP genes including Frizzled (Fz), Flamingo (Fmi), Van Gogh (Vang), Dishevelled (Dsh), Prickle (Pk) and Diego (Dgo), whose products become asymmetrically localized in the cell upon initiation of PCP (reviewed Maung and Jenny, 2011). Subsequent studies in vertebrates have shown that many of these PCP genes are conserved.
Unlike in Drosophila, where the upstream signal for the PCP pathway has not been defined, in vertebrates, a number of so-called 'non-canonical' WNTs have been shown to have roles in PCP processes. WNT5B and WNT11 are both required for CE during gastrulation, and WNT5A physically and genetically interacts with VANGL2 in the inner ear and the developing limb bud (Heisenberg et al, 2000; Rauch et al, 1997; Qian et al, 2007; Gao et al, 2011). WNT ligand can be bound by one of a number of FZD receptors or the single pass transmembrane proteins RYK or ROR, depending on context (reviewed in Green et al, 2008; Fradkin et al, 2010). Although the downstream pathway is not well established, vertebrate PCP signaling appears to work at least in part through DVL, DAAM1 and small GTPases to remodel the actin cytoskeleton (reviewed in Lai et al, 2009; Gao et al, 2012).

Literature References

PubMed ID	Title	Journal	Year
19365405	Wnt/Fz signaling and the cytoskeleton: potential roles in tumorigenesis Chien, AJ, Lai, SL, Moon, RT	Cell Res.	2009
17433286	Wnt5a functions in planar cell polarity regulation in mice Dai, X, Zhang, X, Jones, C, Qian, D, Rzadzinska, A, Chen, P, Steel, KP, Mark, S	Dev. Biol.	2007
19204114	Wnt signaling pathways meet Rho GTPases Hall, A, Schlessinger, K, Tolwinski, N	Genes Dev.	2009
21983142	Planar cell polarity in Drosophila Maung, SM, Jenny, A	Organogenesis	2011
9598355	Wnt5 is required for tail formation in the zebrafish embryo Blader, P, Schauerte, HE, Strähle, U, Rauch, GJ, McMahon, AP, Haffter, P, Hammerschmidt, M, Ingham, PW	Cold Spring Harb. Symp. Quant. Biol.	1997
20004982	Ryks: new partners for Wnts in the developing and regenerating nervous system Fradkin, LG, Noordermeer, JN, Dura, JM	Trends Neurosci.	2010
10811221	Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation Wilson, SW, Saúde, L, Smith, JC, Rauch, GJ, Tada, M, Geisler, R, Stemple, DL, Concha, ML, Heisenberg, CP	Nature	2000
23140633	Wnt regulation of planar cell polarity (PCP) Gao, B	Curr. Top. Dev. Biol.	2012
18848778	Ror receptor tyrosine kinases: orphans no more Green, JL, Sternberg, PW, Kuntz, SG	Trends Cell Biol.	2008