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Dev Biol 2015 Dec 15;4082:316-27. doi: 10.1016/j.ydbio.2015.06.013.
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The involvement of PCP proteins in radial cell intercalations during Xenopus embryonic development.

Ossipova O , Chu CW , Fillatre J , Brott BK , Itoh K , Sokol SY .

The planar cell polarity (PCP) pathway orients cells in diverse epithelial tissues in Drosophila and vertebrate embryos and has been implicated in many human congenital defects and diseases, such as ciliopathies, polycystic kidney disease and malignant cancers. During vertebrate gastrulation and neurulation, PCP signaling is required for convergent extension movements, which are primarily driven by mediolateral cell intercalations, whereas the role for PCP signaling in radial cell intercalations has been unclear. In this study, we examine the function of the core PCP proteins Vangl2, Prickle3 (Pk3) and Disheveled in the ectodermal cells, which undergo radial intercalations during Xenopus gastrulation and neurulation. In the epidermis, multiciliated cell (MCC) progenitors originate in the inner layer, but subsequently migrate to the embryo surface during neurulation. We find that the Vangl2/Pk protein complexes are enriched at the apical domain of intercalating MCCs and are essential for the MCC intercalatory behavior. Addressing the underlying mechanism, we identified KIF13B, as a motor protein that binds Disheveled. KIF13B is required for MCC intercalation and acts synergistically with Vangl2 and Disheveled, indicating that it may mediate microtubule-dependent trafficking of PCP proteins necessary for cell shape regulation. In the neural plate, the Vangl2/Pk complexes were also concentrated near the outermost surface of deep layer cells, suggesting a general role for PCP in radial intercalation. Consistent with this hypothesis, the ectodermal tissues deficient in Vangl2 or Disheveled functions contained more cell layers than normal tissues. We propose that PCP signaling is essential for both mediolateral and radial cell intercalations during vertebrate morphogenesis. These expanded roles underscore the significance of vertebrate PCP proteins as factors contributing to a number of diseases, including neural tube defects, tumor metastases, and various genetic syndromes characterized by abnormal migratory cell behaviors.

PubMed ID: 26079437
PMC ID: PMC4810801
Article link: Dev Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cfp dvl1 dvl2 kif13b mcc myc pkm prickle3 rab11a tub vangl2
Antibodies: Ctnnb1 Ab2 Rab11a Ab4 Tuba4b Ab9
Morpholinos: kif13b MO1 prickle3 MO1 prickle3 MO2 ptpn13 MO1 vangl2 MO4

Disease Ontology terms: ciliopathy
Phenotypes: Xla Wt + dvl2{del_1236-2208} (fig.3.f) [+]

Article Images: [+] show captions
References [+] :
Adler, The frizzled/stan pathway and planar cell polarity in the Drosophila wing. 2012, Pubmed