This Title All WIREs
How to cite this WIREs title:
WIREs Dev Biol
Impact Factor: 5.814

Zebrafish models of non‐canonical Wnt/planar cell polarity signalling: fishing for valuable insight into vertebrate polarized cell behavior

Full article on Wiley Online Library:   HTML PDF

Can't access this content? Tell your librarian.

Planar cell polarity (PCP) coordinates the uniform orientation, structure and movement of cells within the plane of a tissue or organ system. It is beautifully illustrated in the polarized arrangement of bristles and hairs that project from specialized cell surfaces of the insect abdomen and wings, and pioneering genetic studies using the fruit fly, Drosophila melanogaster, have defined a core signalling network underlying PCP. This core PCP/non‐canonical Wnt signalling pathway is evolutionarily conserved, and studies in zebrafish have helped transform our understanding of PCP from a peculiarity of polarized epithelia to a more universal cellular property that orchestrates a diverse suite of polarized cell behaviors that are required for normal vertebrate development. Furthermore, application of powerful genetics, embryonic cell‐transplantation, and live‐imaging capabilities afforded by the zebrafish model have yielded novel insights into the establishment and maintenance of vertebrate PCP, over the course of complex and dynamic morphogenetic events like gastrulation and neural tube morphogenesis. Although key questions regarding vertebrate PCP remain, with the emergence of new genome‐editing technologies and the promise of endogenous labeling and Cre/LoxP conditional targeting strategies, zebrafish remains poised to deliver fundamental new insights into the function and molecular dynamic regulation of PCP signalling from embryonic development through to late‐onset phenotypes and adult disease states. WIREs Dev Biol 2017, 6:e267. doi: 10.1002/wdev.267 This article is categorized under: Signaling Pathways > Global Signaling Mechanisms Early Embryonic Development > Gastrulation and Neurulation Nervous System Development > Vertebrates: General Principles
PCP signalling regulates polarized cell movements during gastrulation that shape the vertebrate body axis. (a) On a cellular level, PCP regulates positioning of organelles such as the centriole/microtubule organizing centre, polarization of cell shape and cell protrusive activity, adhesion of the cell to the ECM and its neighbours, and direction of migration. All of this contributes to PCP‐regulated tissue‐level behaviors (b‐e). (b) Mediolateral cell intercalations narrow the tissue laterally and extend it in the anterioposterior direction. (c) During radial intercalations, cells move from one tissue layer into another and this can extend the tissue in any direction. (d) Oriented cell divisions contribute to the extension of the embryonic axis. (e) Dorsally directed migration of lateral mesodermal cells is a main driver of C&E in zebrafish. (f) Combination of these different polarized cell movements within all germ layers during gastrulation results in the narrowing and elongation of the vertebrate embryonic body axis.
[ Normal View | Magnified View ]
Schematic of core PCP signalling in the fly wing. Fz and Vang interact on the membranes of opposing cells whereas Fmi is present symmetrically on both membranes. Antagonistic intracellular interactions between Vang‐Pk and Fz‐Dsh complexes establish a negative feedback loop that contributes to the asymmetric distribution of PCP signalling components, as well as localized activation of downstream signalling cascades. Genetic mosaic analyses in the fly demonstrate both a cell autonomous and nonautonomous function for PCP signals. PCP mutant cells show polarity defects and can also redirect polarity of surrounding wild‐type cells. For instance clones of cells mutant for Fz orient their neighbours to point towards the clone, whereas Vang mutant clones orient their neighbours to point away from the clone. These observations suggest that local membrane interactions between PCP signalling components lie upstream of observed cellular asymmetries.
[ Normal View | Magnified View ]
PCP signals polarize the microtubule cytoskeleton. (a) PCP regulates mitotic spindle orientation along the animal‐vegetal axis in dorsal epiblast cells at gastrulation. (b) Basal bodies are docked along the posterior apical surface of neural floorplate cells (arrows) in a PCP‐dependent manner. (c) Similarly, posterior tilting of motile cilia on floorplate cells (arrows) is regulated by PCP. Panels (b) and (c) reprinted with permission from Ref . Copyright 2010 Nature Publishing Group.
[ Normal View | Magnified View ]
Phenotypes associated with zebrafish PCP signalling defects. (a) Zebrafish PCP mutants exhibit a shortened (lateral view) and widened (dorsal view) body axis compared to wild‐type (WT) at 24 hpf (hours post fertilization). (b) Whole‐mount RNA in situ hybridization with krox20 (hindbrain) and myoD (somites) illustrates the shortened and widened axis of a PCP mutant at 14hpf (image courtesy of Curtis Boswell). (c) PCP mutants exhibit an increased angle of body axis extension over the yolk at 12‐somite stage. (d) ntl and dlx3 expression in tail‐bud staged WT and PCP mutant embryos highlight C&E defects associated with the notochord and neural plate, respectively. (e) A decreased length‐width ratio of mRFP‐labeled dorsal ectodermal cells in PCP mutants can be measured at 90% epiboly. (f) Scatter‐labeling shows cells undergoing cross‐divisions across the neural tube midline (red and green cells across the dashed line) in wild‐type embryos. In zebrafish PCP mutants, neuroepithelial cells also fail to cross the midline after division (no mixing of red and green cells) and accumulate ectopically within the neural tube. Of note, neural tube closure defects are a hallmark of mammalian PCP signalling mutants, and have been well documented on both mouse models and human genetic studies. (g) PCP also controls the migration of facial branchiomotor neurons (FBMNs) from rhombomere 4 to 6, which fails in mutant embryos. (h) Localization of GFP‐Prickle along the anterior membrane of notochord cells (Reprinted with permission from Ref . Copyright 2006 Nature Publishing Group). (i) Localization of GFP‐Vangl2 to the lateral surfaces of floorplate cells, with enrichment at the anterior apical membrane (arrowhead). Arrow points to the anterior. PCP mutants: (a, c) vangl2/trilobite, (b, d, e) MZptk7, (g) MZvangl2.
[ Normal View | Magnified View ]

Browse by Topic

Signaling Pathways > Global Signaling Mechanisms
Nervous System Development > Vertebrates: General Principles
Early Embryonic Development > Gastrulation and Neurulation