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Shaping the nervous system: role of the core planar cell polarity genes

Nature Reviews Neuroscience volume 14, pages 525–535 (2013)Cite this article

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Key Points

  • Planar cell polarity (PCP) is an established feature of cell sheets that has been studied for decades in flies and more recently in vertebrates. In addition to their role in the skin and inner ear, core PCP genes regulate a number of processes that do not qualify as PCP sensu stricto, particularly during neural development.

  • PCP has a critical role in neural tube closure. This is firmly established by observations that mutations in PCP genes in humans and mice, as well as in fish models, result in neural tube defects. Pathophysiological mechanisms implicate defective convergent extension and neural tube shaping before folding and closure.

  • PCP is also a key regulator of cilia organization in multiciliated cells, particularly in ependymal cells that cover cerebral ventricles. PCP genes regulate both rotational polarity and translational polarity, and defective ependymal PCP results in hydrocephalus.

  • The role of PCP genes in neuronal migration is best understood in the case of facial branchiomotor neurons in the brainstem, which has been studied in fish and mice. There, PCP genes act via complex mechanisms to directly affect migrating neurons as well as altering the organization of their neuroepithelial environment; the latter effect may also involve soluble factors such as non-canonical WNT proteins.

  • Both in mammals and flies, some PCP genes are crucial for axon navigation. Again, this effect may also involve non-canonical WNTs. PCP proteins are required in growing axons as well as in cells that act as intermediate targets or guidepost cells. PCP genes also regulate the mapping of non-overlapping areas by dendrites from adjacent neurons (tiling) or from a given neuron (self-avoidance).

Abstract

Planar cell polarity (PCP) is complementary to the intrinsic polarization of single cells and refers to the global coordination of cell behaviour in the plane of a tissue and, by extension, to the signalling pathways that control it. PCP is most evident in cell sheets, and research into PCP was for years confined to studies in Drosophila melanogaster. However, PCP has more recently emerged as an important phenomenon in vertebrates, in which it regulates various developmental processes and is associated with multiple disorders. In particular, core PCP genes are crucial for the development and function of the nervous system. They are involved in neural tube closure, ependymal polarity, neuronal migration, dendritic growth and axon guidance.

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Figure 1: Core PCP proteins.
Figure 2: PCP and neural tube closure.
Figure 3: PCP and cilia.
Figure 4: PCP and neuronal migration.
Figure 5: PCP and axon guidance.

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References

  1. Ambegaonkar, A. A., Pan, G., Mani, M., Feng, Y. & Irvine, K. D. Propagation of Dachsous-Fat planar cell polarity. Curr. Biol. 22, 1302–1308 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Brittle, A., Thomas, C. & Strutt, D. Planar polarity specification through asymmetric subcellular localization of Fat and Dachsous. Curr. Biol. 22, 907–914 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Vinson, C. R. & Adler, P. N. Directional non-cell autonomy and the transmission of polarity information by the frizzled gene of Drosophila. Nature 329, 549–551 (1987).

    Article  CAS  PubMed  Google Scholar 

  4. Krasnow, R. E., Wong, L. L. & Adler, P. N. dishevelled is a component of the frizzled signaling pathway in Drosophila. Development 121, 4095–4102 (1995).

    CAS  PubMed  Google Scholar 

  5. Taylor, J., Abramova, N., Charlton, J. & Adler, P. N. Van Gogh: a new Drosophila tissue polarity gene. Genetics 150, 199–210 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Chae, J. et al. The Drosophila tissue polarity gene starry night encodes a member of the protocadherin family. Development 126, 5421–5429 (1999).

    CAS  PubMed  Google Scholar 

  7. Usui, T. et al. Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled. Cell 98, 585–595 (1999). References 6 and 7 are the first studies to identify Fmi as a core member of the PCP signalling pathway in flies.

    Article  CAS  PubMed  Google Scholar 

  8. Feiguin, F., Hannus, M., Mlodzik, M. & Eaton, S. The ankyrin repeat protein Diego mediates Frizzled-dependent planar polarization. Dev. Cell 1, 93–101 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Wolff, T. & Rubin, G. M. strabismus, a novel gene that regulates tissue polarity and cell fate decisions in Drosophila. Development 125, 1149–1159 (1998).

    CAS  PubMed  Google Scholar 

  10. Shimada, Y., Yonemura, S., Ohkura, H., Strutt, D. & Uemura, T. Polarized transport of Frizzled along the planar microtubule arrays in Drosophila wing epithelium. Dev. Cell 10, 209–222 (2006).

    Article  CAS  PubMed  Google Scholar 

  11. Guo, Y., Zanetti, G. & Schekman, R. A novel GTP-binding protein-adaptor protein complex responsible for export of Vangl2 from the trans Golgi network. Elife 2, e00160 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Giese, A. P. et al. Gipc1 has a dual role in Vangl2 trafficking and hair bundle integrity in the inner ear. Development 139, 3775–3785 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Das, G., Jenny, A., Klein, T. J., Eaton, S. & Mlodzik, M. Diego interacts with Prickle and Strabismus/Van Gogh to localize planar cell polarity complexes. Development 131, 4467–4476 (2004).

    Article  CAS  PubMed  Google Scholar 

  14. Adler, P. N. Planar signaling and morphogenesis in Drosophila. Dev. Cell 2, 525–535 (2002).

    Article  CAS  PubMed  Google Scholar 

  15. Goodrich, L. V. & Strutt, D. Principles of planar polarity in animal development. Development 138, 1877–1892 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Klein, T. J. & Mlodzik, M. Planar cell polarization: an emerging model points in the right direction. Annu. Rev. Cell Dev. Biol. 21, 155–176 (2005).

    Article  CAS  PubMed  Google Scholar 

  17. Lawrence, P. A., Struhl, G. & Casal, J. Planar cell polarity: one or two pathways? Nature Rev. Genet. 8, 555–563 (2007).

    Article  CAS  PubMed  Google Scholar 

  18. Tissir, F. & Goffinet, A. M. Planar cell polarity signaling in neural development. Curr. Opin. Neurobiol. 20, 572–577 (2010).

    Article  CAS  PubMed  Google Scholar 

  19. Wallingford, J. B. Planar cell polarity and the developmental control of cell behavior in vertebrate embryos. Annu. Rev. Cell Dev. Biol. 28, 627–653 (2012).

    Article  CAS  PubMed  Google Scholar 

  20. Eaton, S. & Julicher, F. Cell flow and tissue polarity patterns. Curr. Opin. Genet. Dev. 21, 747–752 (2011).

    Article  CAS  PubMed  Google Scholar 

  21. Vichas, A. & Zallen, J. A. Translating cell polarity into tissue elongation. Semin. Cell Dev. Biol. 22, 858–864 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Strutt, D. I., Weber, U. & Mlodzik, M. The role of RhoA in tissue polarity and Frizzled signalling. Nature 387, 292–295 (1997).

    Article  CAS  PubMed  Google Scholar 

  23. Lu, B., Usui, T., Uemura, T., Jan, L. & Jan, Y. N. Flamingo controls the planar polarity of sensory bristles and asymmetric division of sensory organ precursors in Drosophila. Curr. Biol. 9, 1247–1250 (1999).

    Article  CAS  PubMed  Google Scholar 

  24. Bellaiche, Y., Gho, M., Kaltschmidt, J. A., Brand, A. H. & Schweisguth, F. Frizzled regulates localization of cell-fate determinants and mitotic spindle rotation during asymmetric cell division. Nature Cell Biol. 3, 50–57 (2001). This study was the first to show that Fz regulates the polarity of the sensory organ precursor cells, and is required for the spindle rotation and asymmetric partition of protein polarity complexes.

    Article  CAS  PubMed  Google Scholar 

  25. Gray, R. S., Roszko, I. & Solnica-Krezel, L. Planar cell polarity: coordinating morphogenetic cell behaviors with embryonic polarity. Dev. Cell 21, 120–133 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ezan, J. & Montcouquiol, M. Revisiting planar cell polarity in the inner ear. Semin. Cell Dev. Biol. 24, 499–506 (2013).

    Article  PubMed  Google Scholar 

  27. Devenport, D. & Fuchs, E. Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles. Nature Cell Biol. 10, 1257–1268 (2008).

    Article  CAS  PubMed  Google Scholar 

  28. Devenport, D., Oristian, D., Heller, E. & Fuchs, E. Mitotic internalization of planar cell polarity proteins preserves tissue polarity. Nature Cell Biol. 13, 893–902 (2011).

    Article  CAS  PubMed  Google Scholar 

  29. Guo, N., Hawkins, C. & Nathans, J. Frizzled6 controls hair patterning in mice. Proc. Natl Acad. Sci. USA 101, 9277–9281 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ravni, A., Qu, Y., Goffinet, A. M. & Tissir, F. Planar cell polarity cadherin Celsr1 regulates skin hair patterning in the mouse. J. Invest. Dermatol. 129, 2507–2509 (2009).

    Article  CAS  PubMed  Google Scholar 

  31. Chang, H. & Nathans, J. Responses of hair follicle-associated structures to loss of planar cell polarity signaling. Proc. Natl Acad. Sci. USA 110, e908–e917 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Wang, Y. & Nathans, J. Tissue/planar cell polarity in vertebrates: new insights and new questions. Development 134, 647–658 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Gao, F. B., Kohwi, M., Brenman, J. E., Jan, L. Y. & Jan, Y. N. Control of dendritic field formation in Drosophila: the roles of flamingo and competition between homologous neurons. Neuron 28, 91–101 (2000).

    Article  CAS  PubMed  Google Scholar 

  34. Senti, K. A. et al. Flamingo regulates R8 axon–axon and axon–target interactions in the Drosophila visual system. Curr. Biol. 13, 828–832 (2003).

    Article  CAS  PubMed  Google Scholar 

  35. Fenstermaker, A. G. et al. Wnt/planar cell polarity signaling controls the anterior-posterior organization of monoaminergic axons in the brainstem. J. Neurosci. 30, 16053–16064 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Tissir, F., Bar, I., Jossin, Y., De Backer, O. & Goffinet, A. M. Protocadherin Celsr3 is crucial in axonal tract development. Nature Neurosci. 8, 451–457 (2005). References 36 and 37 report that loss of CELSR3 and FZD3 results in profuse anomalies of cerebral axonal tarcts, implicating these proteins in axon guidance in the mammalian brain for the first time.

    Article  CAS  PubMed  Google Scholar 

  37. Wang, Y., Thekdi, N., Smallwood, P. M., Macke, J. P. & Nathans, J. Frizzled-3 is required for the development of major fiber tracts in the rostral CNS. J. Neurosci. 22, 8563–8573 (2002). This paper showed the key role of FZD3 in axon guidance in the mouse CNS and thus provides the first in vivo evidence for the role of PCP in axon pathfinding. This received a strong support from the study in reference 36, showing a very similar role of CELSR3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bingham, S., Higashijima, S., Okamoto, H. & Chandrasekhar, A. The zebrafish trilobite gene is essential for tangential migration of branchiomotor neurons. Dev. Biol. 242, 149–160 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Jessen, J. R. et al. Zebrafish trilobite identifies new roles for Strabismus in gastrulation and neuronal movements. Nature Cell Biol. 4, 610–615 (2002). References 38 and 39 showed that facial motor neurons fail to migrate out of r4 in Vangl2-mutant zebrafish.

    Article  CAS  PubMed  Google Scholar 

  40. Rohrschneider, M. R., Elsen, G. E. & Prince, V. E. Zebrafish Hoxb1a regulates multiple downstream genes including prickle1b. Dev. Biol. 309, 358–372 (2007).

    Article  CAS  PubMed  Google Scholar 

  41. Carreira-Barbosa, F. et al. Prickle 1 regulates cell movements during gastrulation and neuronal migration in zebrafish. Development 130, 4037–4046 (2003).

    Article  CAS  PubMed  Google Scholar 

  42. Wada, H., Tanaka, H., Nakayama, S., Iwasaki, M. & Okamoto, H. Frizzled3a and Celsr2 function in the neuroepithelium to regulate migration of facial motor neurons in the developing zebrafish hindbrain. Development 133, 4749–4759 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Qu, Y. B. et al. Atypical cadherins Celsr1-3 differentially regulate migration of facial branchiomotor neurons in mice. J. Neurosci. 30, 9392–9401 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Vivancos, V. et al. Wnt activity guides facial branchiomotor neuron migration, and involves the PCP pathway and JNK and ROCK kinases. Neural Dev. 4, 7 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Glasco, D. M. et al. The mouse Wnt/PCP protein Vangl2 is necessary for migration of facial branchiomotor neurons, and functions independently of Dishevelled. Dev. Biol. 369, 211–222 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Greene, N. D. & Copp, A. J. Development of the vertebrate central nervous system: formation of the neural tube. Prenat. Diagn. 29, 303–311 (2009).

    Article  CAS  PubMed  Google Scholar 

  47. Wang, J. et al. Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation. Development 133, 1767–1778 (2006).

    Article  CAS  PubMed  Google Scholar 

  48. Ybot-Gonzalez, P. et al. Convergent extension, planar-cell-polarity signalling and initiation of mouse neural tube closure. Development 134, 789–799 (2007).

    Article  CAS  PubMed  Google Scholar 

  49. Heisenberg, C. P. et al. Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. Nature 405, 76–81 (2000).

    Article  CAS  PubMed  Google Scholar 

  50. Tada, M. & Smith, J. C. Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway. Development 127, 2227–2238 (2000).

    CAS  PubMed  Google Scholar 

  51. Wallingford, J. B. et al. Dishevelled controls cell polarity during Xenopus gastrulation. Nature 405, 81–85 (2000).

    Article  CAS  PubMed  Google Scholar 

  52. Wallingford, J. B. & Harland, R. M. Neural tube closure requires Dishevelled-dependent convergent extension of the midline. Development 129, 5815–5825 (2002).

    Article  CAS  PubMed  Google Scholar 

  53. Kibar, Z. et al. Ltap, a mammalian homolog of Drosophila Strabismus/Van Gogh, is altered in the mouse neural tube mutant Loop-tail. Nature Genet. 28, 251–255 (2001). References 53 and 59 demonstrated that the looptail mutation, which results in NTDs, is in the Vangl2 gene, implicating a PCP-related process in neural development for the first time. References 54–58 showed that other PCP genes are also essential for neural tube closure.

    Article  CAS  PubMed  Google Scholar 

  54. Wang, Y., Guo, N. & Nathans, J. The role of Frizzled3 and Frizzled6 in neural tube closure and in the planar polarity of inner-ear sensory hair cells. J. Neurosci. 26, 2147–2156 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Lee, J. et al. PTK7 regulates myosin II activity to orient planar polarity in the mammalian auditory epithelium. Curr. Biol. 22, 956–966 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lu, X. et al. PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. Nature 430, 93–98 (2004).

    Article  CAS  PubMed  Google Scholar 

  57. Hamblet, N. S. et al. Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure. Development 129, 5827–5838 (2002).

    Article  CAS  PubMed  Google Scholar 

  58. Curtin, J. A. et al. Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. Curr. Biol. 13, 1129–1133 (2003). Using ENU ( N -ethyl- N -nitrosourea) mutagenesis, this study identified two point mutations in the Celsr1 gene, which is present in crash and spin cycle mutant mice, that lead to open neural tube and inner ear anomalies. This was the first demonstration that the CELSR family is a key player in PCP in mice.

    Article  CAS  PubMed  Google Scholar 

  59. Murdoch, J. N., Doudney, K., Paternotte, C., Copp, A. J. & Stanier, P. Severe neural tube defects in the loop-tail mouse result from mutation of Lpp1, a novel gene involved in floor plate specification. Hum. Mol. Genet. 10, 2593–2601 (2001).

    Article  CAS  PubMed  Google Scholar 

  60. Juriloff, D. M. & Harris, M. J. A consideration of the evidence that genetic defects in planar cell polarity contribute to the etiology of human neural tube defects. Birth Defects Res. A Clin. Mol. Teratol. 94, 824–840 (2012).

    Article  CAS  PubMed  Google Scholar 

  61. Allache, R., De Marco, P., Merello, E., Capra, V. & Kibar, Z. Role of the planar cell polarity gene CELSR1 in neural tube defects and caudal agenesis. Birth Defects Res. A Clin. Mol. Teratol. 94, 176–181 (2012).

    Article  CAS  PubMed  Google Scholar 

  62. Doudney, K. et al. Analysis of the planar cell polarity gene Vangl2 and its co-expressed paralogue Vangl1 in neural tube defect patients. Am. J. Med. Genet. A 136A, 90–92 (2005).

    Article  Google Scholar 

  63. Robinson, A. et al. Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect craniorachischisis. Hum. Mutat. 33, 440–447 (2012).

    Article  CAS  PubMed  Google Scholar 

  64. Kibar, Z. et al. Mutations in VANGL1 associated with neural-tube defects. N. Engl. J. Med. 356, 1432–1437 (2007).

    Article  CAS  PubMed  Google Scholar 

  65. Bosoi, C. M. et al. Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects. Hum. Mutat. 32, 1371–1375 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. De Marco, P. et al. FZD6 is a novel gene for human neural tube defects. Hum. Mutat. 33, 384–390 (2012).

    Article  CAS  PubMed  Google Scholar 

  67. Ciruna, B., Jenny, A., Lee, D., Mlodzik, M. & Schier, A. F. Planar cell polarity signalling couples cell division and morphogenesis during neurulation. Nature 439, 220–224 (2006). This paper shows that the PCP protein Vangl2 is involved in the neural tube closure and affects both cell intercalation and division in zebrafish.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Nishimura, T., Honda, H. & Takeichi, M. Planar cell polarity links axes of spatial dynamics in neural-tube closure. Cell 149, 1084–1097 (2012).

    Article  CAS  PubMed  Google Scholar 

  69. Merte, J. et al. Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure. Nature Cell Biol. 12, 41–46 (2010).

    Article  CAS  PubMed  Google Scholar 

  70. Wansleeben, C. et al. Planar cell polarity defects and defective Vangl2 trafficking in mutants for the COPII gene Sec24b. Development 137, 1067–1073 (2010).

    Article  CAS  PubMed  Google Scholar 

  71. Yang, X. Y. et al. Mutations in the COPII vesicle component gene SEC24B are associated with human neural tube defects. Hum. Mutat. http://dx.doi.org/10.1002/humu.22338 (2013).

  72. Segalen, M. & Bellaiche, Y. Cell division orientation and planar cell polarity pathways. Semin. Cell Dev. Biol. 20, 972–977 (2009).

    Article  CAS  PubMed  Google Scholar 

  73. Gong, Y., Mo, C. & Fraser, S. E. Planar cell polarity signalling controls cell division orientation during zebrafish gastrulation. Nature 430, 689–693 (2004).

    Article  CAS  PubMed  Google Scholar 

  74. Segalen, M. et al. The Fz–Dsh planar cell polarity pathway induces oriented cell division via Mud/NuMA in Drosophila and zebrafish. Dev. Cell 19, 740–752 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Lake, B. B. & Sokol, S. Y. Strabismus regulates asymmetric cell divisions and cell fate determination in the mouse brain. J. Cell Biol. 185, 59–66 (2009). This work shows that in mice, the looptail mutation in Vangl2 affects the mitotic spindle orientation and has an impact on cell fate determination and lamination of the cerebral cortex.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Wallingford, J. B. & Mitchell, B. Strange as it may seem: the many links between Wnt signaling, planar cell polarity, and cilia. Genes Dev. 25, 201–213 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Eley, L., Yates, L. M. & Goodship, J. A. Cilia and disease. Curr. Opin. Genet. Dev. 15, 308–314 (2005).

    Article  CAS  PubMed  Google Scholar 

  78. Davenport, J. R. & Yoder, B. K. An incredible decade for the primary cilium: a look at a once-forgotten organelle. Am. J. Physiol. Renal Physiol. 289, F1159–F1169 (2005).

    Article  CAS  PubMed  Google Scholar 

  79. Song, H. et al. Planar cell polarity breaks bilateral symmetry by controlling ciliary positioning. Nature 466, 378–382 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Marshall, W. F. & Kintner, C. Cilia orientation and the fluid mechanics of development. Curr. Opin. Cell Biol. 20, 48–52 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Wallingford, J. B. Planar cell polarity signaling, cilia and polarized ciliary beating. Curr. Opin. Cell Biol. 22, 597–604 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Voronina, V. A. et al. Inactivation of Chibby affects function of motile airway cilia. J. Cell Biol. 185, 225–233 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Tissir, F. et al. Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus. Nature Neurosci. 13, 700–707 (2010). This work reports the importance of CELSR2 and CELSR3 in ependymal ciliogenesis and cilia polarity, and outlines the link between PCP, ependymal cilia and hydrocephalus.

    Article  CAS  PubMed  Google Scholar 

  84. Guirao, B. et al. Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia. Nature Cell Biol. 12, 341–350 (2010).

    Article  CAS  PubMed  Google Scholar 

  85. Mitchell, B., Jacobs, R., Li, J., Chien, S. & Kintner, C. A positive feedback mechanism governs the polarity and motion of motile cilia. Nature 447, 97–101 (2007).

    Article  CAS  PubMed  Google Scholar 

  86. Mirzadeh, Z., Han, Y. G., Soriano-Navarro, M., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Cilia organize ependymal planar polarity. J. Neurosci. 30, 2600–2610 (2010). Using en face preparations of the lateral ventricle, developed by the same team, this work introduces the very useful concepts of rotational and translational polarities in ependymal cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Park, T. J., Haigo, S. L. & Wallingford, J. B. Ciliogenesis defects in embryos lacking inturned or fuzzy function are associated with failure of planar cell polarity and Hedgehog signaling. Nature Genet. 38, 303–311 (2006).

    Article  CAS  PubMed  Google Scholar 

  88. Park, T. J., Mitchell, B. J., Abitua, P. B., Kintner, C. & Wallingford, J. B. Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells. Nature Genet. 40, 871–879 (2008). This work, together with references 87 and 83, demonstrates the role of PCP genes in ciliogenesis and cilia polarity in the ciliated skin of X. laevis.

    Article  CAS  PubMed  Google Scholar 

  89. Mitchell, B. et al. The PCP pathway instructs the planar orientation of ciliated cells in the Xenopus larval skin. Curr. Biol. 19, 924–929 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Vladar, E. K., Bayly, R. D., Sangoram, A. M., Scott, M. P. & Axelrod, J. D. Microtubules enable the planar cell polarity of airway cilia. Curr. Biol. 22, 2203–2212 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kunimoto, K. et al. Coordinated ciliary beating requires Odf2-mediated polarization of basal bodies via basal feet. Cell 148, 189–200 (2012).

    Article  CAS  PubMed  Google Scholar 

  92. Werner, M. E. et al. Actin and microtubules drive differential aspects of planar cell polarity in multiciliated cells. J. Cell Biol. 195, 19–26 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Adler, P. N. The frizzled/stan pathway and planar cell polarity in the Drosophila wing. Curr. Top. Dev. Biol. 101, 1–31 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Gault, W. J., Olguin, P., Weber, U. & Mlodzik, M. Drosophila CK1-γ, gilgamesh, controls PCP-mediated morphogenesis through regulation of vesicle trafficking. J. Cell Biol. 196, 605–621 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Sepich, D. S., Usmani, M., Pawlicki, S. & Solnica-Krezel, L. Wnt/PCP signaling controls intracellular position of MTOCs during gastrulation convergence and extension movements. Development 138, 543–552 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Babayeva, S., Zilber, Y. & Torban, E. Planar cell polarity pathway regulates actin rearrangement, cell shape, motility, and nephrin distribution in podocytes. Am. J. Physiol. Renal Physiol. 300, F549–F560 (2011).

    Article  CAS  PubMed  Google Scholar 

  97. Habas, R., Kato, Y. & He, X. Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1. Cell 107, 843–854 (2001).

    Article  CAS  PubMed  Google Scholar 

  98. Hirota, Y. et al. Planar polarity of multiciliated ependymal cells involves the anterior migration of basal bodies regulated by non-muscle myosin II. Development 137, 3037–3046 (2010).

    Article  CAS  PubMed  Google Scholar 

  99. Axelrod, J. D., Miller, J. R., Shulman, J. M., Moon, R. T. & Perrimon, N. Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways. Genes Dev. 12, 2610–2622 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Yasunaga, T., Itoh, K. & Sokol, S. Y. Regulation of basal body and ciliary functions by Diversin. Mech. Dev. 128, 376–386 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Ross, A. J. et al. Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nature Genet. 37, 1135–1140 (2005).

    Article  CAS  PubMed  Google Scholar 

  102. Olguin, P., Glavic, A. & Mlodzik, M. Intertissue mechanical stress affects Frizzled-mediated planar cell polarity in the Drosophila notum epidermis. Curr. Biol. 21, 236–242 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Aigouy, B. et al. Cell flow reorients the axis of planar polarity in the wing epithelium of Drosophila. Cell 142, 773–786 (2010). This paper shows that, in the D. melanogaster wing, PCP initially has a radial orientation that realigns along the proximal–distal axis by mechanical forces and cell rearrangements. It also uses an original modelling approach using nematics liquid crystals to represent polarized elements in a sheet.

    Article  CAS  PubMed  Google Scholar 

  104. Banizs, B. et al. Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus. Development 132, 5329–5339 (2005).

    Article  CAS  PubMed  Google Scholar 

  105. Ibañez-Tallon, I. et al. Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation. Hum. Mol. Genet. 13, 2133–2141 (2004).

    Article  PubMed  Google Scholar 

  106. Lechtreck, K. F., Delmotte, P., Robinson, M. L., Sanderson, M. J. & Witman, G. B. Mutations in Hydin impair ciliary motility in mice. J. Cell Biol. 180, 633–643 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Town, T. et al. The stumpy gene is required for mammalian ciliogenesis. Proc. Natl Acad. Sci. USA 105, 2853–2858 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Ibañez-Tallon, I., Heintz, N. & Omran, H. To beat or not to beat: roles of cilia in development and disease. Hum. Mol. Genet. 12, R27–R35 (2003).

    Article  CAS  PubMed  Google Scholar 

  109. Chandrasekhar, A. Turning heads: development of vertebrate branchiomotor neurons. Dev. Dyn. 229, 143–161 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Garel, S., Garcia-Dominguez, M. & Charnay, P. Control of the migratory pathway of facial branchiomotor neurones. Development 127, 5297–5307 (2000).

    CAS  PubMed  Google Scholar 

  111. Guthrie, S. Patterning and axon guidance of cranial motor neurons. Nature Rev. Neurosci. 8, 859–871 (2007).

    Article  CAS  Google Scholar 

  112. Song, M. R. et al. T-Box transcription factor Tbx20 regulates a genetic program for cranial motor neuron cell body migration. Development 133, 4945–4955 (2006).

    Article  CAS  PubMed  Google Scholar 

  113. Goffinet, A. M. Abnormal development of the facial nerve nucleus in reeler mutant mice. J. Anat. 138, 207–215 (1984).

    PubMed  PubMed Central  Google Scholar 

  114. Gilland, E. & Baker, R. Evolutionary patterns of cranial nerve efferent nuclei in vertebrates. Brain Behav. Evol. 66, 234–254 (2005).

    Article  PubMed  Google Scholar 

  115. Walsh, G. S., Grant, P. K., Morgan, J. A. & Moens, C. B. Planar polarity pathway and Nance-Horan syndrome-like 1b have essential cell-autonomous functions in neuronal migration. Development 138, 3033–3042 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Mapp, O. M., Wanner, S. J., Rohrschneider, M. R. & Prince, V. E. Prickle1b mediates interpretation of migratory cues during zebrafish facial branchiomotor neuron migration. Dev. Dyn. 239, 1596–1608 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Formstone, C. J. 7TM-Cadherins: developmental roles and future challenges. Adv. Exp. Med. Biol. 706, 14–36 (2010).

    Article  CAS  PubMed  Google Scholar 

  118. Ying, G. et al. The protocadherin gene Celsr3 is required for interneuron migration in the mouse forebrain. Mol. Cell. Biol. 29, 3045–3061 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Stockinger, P., Maitre, J. L. & Heisenberg, C. P. Defective neuroepithelial cell cohesion affects tangential branchiomotor neuron migration in the zebrafish neural tube. Development 138, 4673–4683 (2011).

    Article  CAS  PubMed  Google Scholar 

  120. Wanner, S. J. & Prince, V. E. Axon tracts guide zebrafish facial branchiomotor neuron migration through the hindbrain. Development 140, 906–915 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Formstone, C. J., Moxon, C., Murdoch, J., Little, P. & Mason, I. Basal enrichment within neuroepithelia suggests novel function(s) for Celsr1 protein. Mol. Cell Neurosci. 44, 210–222 (2010).

    Article  CAS  PubMed  Google Scholar 

  122. Reuter, J. E. et al. A mosaic genetic screen for genes necessary for Drosophila mushroom body neuronal morphogenesis. Development 130, 1203–1213 (2003).

    Article  CAS  PubMed  Google Scholar 

  123. Kimura, H., Usui, T., Tsubouchi, A. & Uemura, T. Potential dual molecular interaction of the Drosophila 7-pass transmembrane cadherin Flamingo in dendritic morphogenesis. J. Cell Sci. 119, 1118–1129 (2006).

    Article  CAS  PubMed  Google Scholar 

  124. Matsubara, D., Horiuchi, S. Y., Shimono, K., Usui, T. & Uemura, T. The seven-pass transmembrane cadherin Flamingo controls dendritic self-avoidance via its binding to a LIM domain protein, Espinas, in Drosophila sensory neurons. Genes Dev. 25, 1982–1996 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Shima, Y., Kengaku, M., Hirano, T., Takeichi, M. & Uemura, T. Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin. Dev. Cell 7, 205–216 (2004).

    Article  CAS  PubMed  Google Scholar 

  126. Shima, Y. et al. Opposing roles in neurite growth control by two seven-pass transmembrane cadherins. Nature Neurosci. 10, 963–969 (2007).

    Article  CAS  PubMed  Google Scholar 

  127. Chen, P. L. & Clandinin, T. R. The cadherin Flamingo mediates level-dependent interactions that guide photoreceptor target choice in Drosophila. Neuron 58, 26–33 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Lee, R. C. et al. The protocadherin Flamingo is required for axon target selection in the Drosophila visual system. Nature Neurosci. 6, 557–563 (2003). This work, together with that in reference 34, identifies Fmi as a key player in axon guidance and in target selection in the D. melanogaster visual system.

    Article  CAS  PubMed  Google Scholar 

  129. Hakeda-Suzuki, S. et al. Golden Goal collaborates with Flamingo in conferring synaptic-layer specificity in the visual system. Nature Neurosci. 14, 314–323 (2011).

    Article  CAS  PubMed  Google Scholar 

  130. Mrkusich, E. M., Flanagan, D. J. & Whitington, P. M. The core planar cell polarity gene prickle interacts with flamingo to promote sensory axon advance in the Drosophila embryo. Dev. Biol. 358, 224–230 (2011).

    Article  CAS  PubMed  Google Scholar 

  131. Shimizu, K., Sato, M. & Tabata, T. The Wnt5/planar cell polarity pathway regulates axonal development of the Drosophila mushroom body neuron. J. Neurosci. 31, 4944–4954 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Ng, J. Wnt/PCP proteins regulate stereotyped axon branch extension in Drosophila. Development 139, 165–177 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Steimel, A. et al. The Flamingo ortholog FMI-1 controls pioneer-dependent navigation of follower axons in C. elegans. Development 137, 3663–3673 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Huarcaya Najarro, E. & Ackley, B. D. C. elegans fmi-1/flamingo and Wnt pathway components interact genetically to control the anteroposterior neurite growth of the VD GABAergic neurons. Dev. Biol. 377, 224–235 (2013).

    Article  CAS  PubMed  Google Scholar 

  135. Najarro, E. H. et al. Caenorhabditis elegans flamingo cadherin fmi-1 regulates GABAergic neuronal development. J. Neurosci. 32, 4196–4211 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Bassuk, A. G. et al. A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome. Am. J. Hum. Genet. 83, 572–581 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Fujimura, L. & Hatano, M. R ole of Prickle1 and Prickle2 in neurite outgrowth in murine neuroblastoma cells. Methods Mol. Biol. 839, 173–185 (2012).

    Article  CAS  PubMed  Google Scholar 

  138. Okuda, H., Miyata, S., Mori, Y. & Tohyama, M. Mouse Prickle1 and Prickle2 are expressed in postmitotic neurons and promote neurite outgrowth. FEBS Lett. 581, 4754–4760 (2007).

    Article  CAS  PubMed  Google Scholar 

  139. Hida, Y. et al. Prickle2 is localized in the postsynaptic density and interacts with PSD-95 and NMDA receptors in the brain. J. Biochem. 149, 693–700 (2011).

    Article  CAS  PubMed  Google Scholar 

  140. Yoshioka, T., Hagiwara, A., Hida, Y. & Ohtsuka, T. Vangl2, the planner cell polarity protein, is complexed with postsynaptic density protein PSD-95. FEBS Lett. 587, 1453–1459 (2013).

    Article  CAS  PubMed  Google Scholar 

  141. Feng, J. et al. A role for atypical cadherin Celsr3 in hippocampal maturation and connectivity. J. Neurosci. 32, 13729–13743 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Price, D. J. et al. The development of cortical connections. Eur. J. Neurosci. 23, 910–920 (2006).

    Article  PubMed  Google Scholar 

  143. Lyuksyutova, A. I. et al. Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling. Science 302, 1984–1988 (2003). This is the first study to show that the WNT and PCP signalling guides spinal cord commissural axons along the anterior–posterior axis after midline crossing.

    Article  CAS  PubMed  Google Scholar 

  144. Shafer, B., Onishi, K., Lo, C., Colakoglu, G. & Zou, Y. Vangl2 promotes Wnt/planar cell polarity-like signaling by antagonizing Dvl1-mediated feedback inhibition in growth cone guidance. Dev. Cell 20, 177–191 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Zhou, L. et al. Early forebrain wiring: genetic dissection using conditional Celsr3 mutant mice. Science 320, 946–949 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Steinel, M. C. & Whitington, P. M. The atypical cadherin Flamingo is required for sensory axon advance beyond intermediate target cells. Dev. Biol. 327, 447–457 (2009). Using regional gene inactivation in vivo , this work shows that forebrain wiring requires Celsr3 expression in guidepost cells. A complementary work (reference 147) demonstrates the role of Fmi in intermediate target for progression of sensory axons in flies.

    Article  CAS  PubMed  Google Scholar 

  147. Sasselli, V. et al. Planar cell polarity genes control the connectivity of enteric neurons. J. Clin. Invest. 123, 1763–1772 (2013). This paper provides the first evidence for the role of core PCP genes in the development of the enteric nervous system in mice and shows that this has physiological implications for gut peristaltic movements.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Xu, Q. et al. Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 116, 883–895 (2004).

    Article  CAS  PubMed  Google Scholar 

  149. Greco, V., Hannus, M. & Eaton, S. Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell 106, 633–645 (2001).

    Article  CAS  PubMed  Google Scholar 

  150. Fevrier, B. & Raposo, G. Exosomes: endosomal-derived vesicles shipping extracellular messages. Curr. Opin. Cell Biol. 16, 415–421 (2004).

    Article  CAS  PubMed  Google Scholar 

  151. Sagner, A. et al. Establishment of global patterns of planar polarity during growth of the Drosophila wing epithelium. Curr. Biol. 22, 1296–1301 (2012).

    Article  CAS  PubMed  Google Scholar 

  152. Heberlein, U., Wolff, T. & Rubin, G. M. The TGF β homolog dpp and the segment polarity gene hedgehog are required for propagation of a morphogenetic wave in the Drosophila retina. Cell 75, 913–926 (1993).

    Article  CAS  PubMed  Google Scholar 

  153. Pourquie, O. Vertebrate segmentation: from cyclic gene networks to scoliosis. Cell 145, 650–663 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Bosveld, F. et al. Mechanical control of morphogenesis by Fat/Dachsous/Four-jointed planar cell polarity pathway. Science 336, 724–727 (2012).

    Article  CAS  PubMed  Google Scholar 

  155. Wang, Y., Chang, H. & Nathans, J. When whorls collide: the development of hair patterns in frizzled 6 mutant mice. Development 137, 4091–4099 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Casal, J., Lawrence, P. A. & Struhl, G. Two separate molecular systems, Dachsous/Fat and Starry night/Frizzled, act independently to confer planar cell polarity. Development 133, 4561–4572 (2006).

    Article  CAS  PubMed  Google Scholar 

  157. Lawrence, P. A., Struhl, G. & Casal, J. Do the protocadherins Fat and Dachsous link up to determine both planar cell polarity and the dimensions of organs? Nature Cell Biol. 10, 1379–1382 (2008).

    Article  CAS  PubMed  Google Scholar 

  158. Amonlirdviman, K. et al. Mathematical modeling of planar cell polarity to understand domineering nonautonomy. Science 307, 423–426 (2005).

    Article  CAS  PubMed  Google Scholar 

  159. Formstone, C. J. & Little, P. F. The flamingo-related mouse Celsr family (Celsr1–3) genes exhibit distinct patterns of expression during embryonic development. Mech. Dev. 109, 91–94 (2001).

    Article  CAS  PubMed  Google Scholar 

  160. Shima, Y. et al. Differential expression of the seven-pass transmembrane cadherin genes Celsr1-3 and distribution of the Celsr2 protein during mouse development. Dev. Dyn. 223, 321–332 (2002).

    Article  CAS  PubMed  Google Scholar 

  161. Tissir, F., De-Backer, O., Goffinet, A. M. & Lambert de Rouvroit, C. Developmental expression profiles of Celsr (Flamingo) genes in the mouse. Mech. Dev. 112, 157–160 (2002).

    Article  CAS  PubMed  Google Scholar 

  162. Tissir, F. & Goffinet, A. M. Expression of planar cell polarity genes during development of the mouse CNS. Eur. J. Neurosci. 23, 597–607 (2006).

    Article  PubMed  Google Scholar 

  163. Dickson, B. J. Molecular mechanisms of axon guidance. Science 298, 1959–1964 (2002).

    Article  CAS  PubMed  Google Scholar 

  164. Turner, C. M. & Adler, P. N. Distinct roles for the actin and microtubule cytoskeletons in the morphogenesis of epidermal hairs during wing development in Drosophila. Mech. Dev. 70, 181–192 (1998).

    Article  CAS  PubMed  Google Scholar 

  165. Wong, L. L. & Adler, P. N. Tissue polarity genes of Drosophila regulate the subcellular location for prehair initiation in pupal wing cells. J. Cell Biol. 123, 209–221 (1993).

    Article  CAS  PubMed  Google Scholar 

  166. Singh, J., Yanfeng, W. A., Grumolato, L., Aaronson, S. A. & Mlodzik, M. Abelson family kinases regulate Frizzled planar cell polarity signaling via Dsh phosphorylation. Genes Dev. 24, 2157–2168 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Yanfeng, W. A. et al. Functional dissection of phosphorylation of Disheveled in Drosophila. Dev. Biol. 360, 132–142 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Liu, W. et al. Mechanism of activation of the Formin protein Daam1. Proc. Natl Acad. Sci. USA 105, 210–215 (2008).

    Article  PubMed  Google Scholar 

  169. Schonichen, A. & Geyer, M. Fifteen formins for an actin filament: a molecular view on the regulation of human formins. Biochim. Biophys. Acta 1803, 152–163 (2010).

    Article  CAS  PubMed  Google Scholar 

  170. Ishikawa, H. O., Takeuchi, H., Haltiwanger, R. S. & Irvine, K. D. Four-jointed is a Golgi kinase that phosphorylates a subset of cadherin domains. Science 321, 401–404 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Sopko, R. et al. Phosphorylation of the tumor suppressor fat is regulated by its ligand Dachsous and the kinase discs overgrown. Curr. Biol. 19, 1112–1117 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Thomas, C. & Strutt, D. The roles of the cadherins Fat and Dachsous in planar polarity specification in Drosophila. Dev. Dyn. 241, 27–39 (2012).

    Article  CAS  PubMed  Google Scholar 

  173. Matakatsu, H. & Blair, S. S. Separating planar cell polarity and Hippo pathway activities of the protocadherins Fat and Dachsous. Development 139, 1498–1508 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Mao, Y. et al. Dachs: an unconventional myosin that functions downstream of Fat to regulate growth, affinity and gene expression in Drosophila. Development 133, 2539–2551 (2006).

    Article  CAS  PubMed  Google Scholar 

  175. Mao, Y. et al. Characterization of a Dchs1 mutant mouse reveals requirements for Dchs1-Fat4 signaling during mammalian development. Development 138, 947–957 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Saburi, S., Hester, I., Goodrich, L. & McNeill, H. Functional interactions between Fat family cadherins in tissue morphogenesis and planar polarity. Development 139, 1806–1820 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Saburi, S. et al. Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease. Nature Genet. 40, 1010–1015 2008).

    Article  CAS  PubMed  Google Scholar 

  178. Backman, M., Machon, O., Van Den Bout, C. J. & Krauss, S. Targeted disruption of mouse Dach1 results in postnatal lethality. Dev. Dyn. 226, 139–144 (2003).

    Article  CAS  PubMed  Google Scholar 

  179. Davis, R. J. et al. Dach1 mutant mice bear no gross abnormalities in eye, limb, and brain development and exhibit postnatal lethality. Mol. Cell. Biol. 21, 1484–1490 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Davis, R. J., Pesah, Y. I., Harding, M., Paylor, R. & Mardon, G. Mouse Dach2 mutants do not exhibit gross defects in eye development or brain function. Genesis 44, 84–92 (2006).

    Article  CAS  PubMed  Google Scholar 

  181. Ciani, L., Patel, A., Allen, N. D. & ffrench-Constant, C. Mice lacking the giant protocadherin mFAT1 exhibit renal slit junction abnormalities and a partially penetrant cyclopia and anophthalmia phenotype. Mol. Cell. Biol. 23, 3575–3582 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Morris, L. G. et al. Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation. Nature Genet. 45, 253–261 (2013).

    Article  CAS  PubMed  Google Scholar 

  183. Barlow, J. L. et al. A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q– syndrome. Nature Med. 16, 59–66 (2010).

    Article  CAS  PubMed  Google Scholar 

  184. Deans, M. R. et al. Control of neuronal morphology by the atypical cadherin Fat3. Neuron 71, 820–832 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Probst, B., Rock, R., Gessler, M., Vortkamp, A. & Puschel, A. W. The rodent Four-jointed ortholog Fjx1 regulates dendrite extension. Dev. Biol. 312, 461–470 (2007).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank C. Boutin, A. Chandrasekhar and Y. Qu for helpful discussions. We apologize to those authors whose work was not covered owing to the limited scope and space constraints. This work was supported by grants FRSM 3.4550.11, Actions de Recherches Concertées (ARC-10/15-026), Fondation médicale Reine Elisabeth (FMRE) to F.T.; and grants FRFC 2.4504.01, FRSM T.0002.13, PAI7/20 from Belspo; and DIANE and Welbio from the Région wallonne to A.M.G. F.T. is a research associate at the Belgian Fonds de la Recherche Scientifique (FNRS).

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    Fadel Tissir & André M. Goffinet

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PowerPoint slides

Glossary

Apicobasal polarity

Refers to the fact that cells (especially epithelial cells) have distinct apical and basolateral domains, a feature controlled by the Par and Crumbs apical complexes, and by the Scribble basolateral complex in flies. Apicobasal polarity is radial to planar cell polarity.

Convergent extension

A process by which a tissue is remodelled during development to become narrow (converge) along one axis and elongate (extend) along the other axis. Examples include the elongation of the notochord and embryonic axis during gastrulation, and the transformation of the neural plate into the neural tube.

Craniorachischisis

The most severe neural tube closure defect in which both the cranium and the rachis are open and exposed to the external milieu. This malformation is incompatible with life.

Myelomeningocele

A localized neural tube closure defect. It is a form of spina bifida that usually occurs in the lumbar region with hernia of the spinal cord (myelo) and meningeal tissue. Myelomeningocele has various degrees of severity and can often be surgically treated.

Adherens junctions

Multiprotein complexes at cell–cell junctions, which are rich in cadherins and other adhesion proteins. Their cytoplasmic side is linked to the actin cytoskeleton by adaptor proteins such as catenins. They form a belt encircling the cell (zonula adherens) or spots of attachment to the extracellular matrix (adhesion plaques).

Vesicle coat protein complex II

(COPII). This complex mediates the anterograde transport of vesicle trafficking from the endoplasmic reticulum to the Golgi.

Morphants

Organisms that have been genetically modified using morpholino oligomers, which modify gene expression by interfering with endogenous RNA.

Endfeet

The dilated extremities of radial glial cells that abut the basal lamina at the pial surface and participate to the so-called 'external limiting' membrane.

Mushroom body

(Also known as corpora pedunculata). A pair of structures in the brain of arthropods that contain specific neurons and associated neuropile (axons and dendrites) as well as glia. It is thought to play a part in olfactory memory and learning.

Guidepost cells

Cells that assist as relays during axonal navigation. They are usually immature neurons but could be glia or other cell types.

Argosomes

Vesicular particles formed by budding from the plasma membrane — in a mechanism reminiscent of that used by retroviruses — that keep surface molecules exposed to the external medium. They are able to transmit morphogen signals at a distance and are very similar if not identical to exosomes.

Domineering non-autonomy

A phenotype seen in mosaic flies in which the presence of a mutant clone perturbs the planar polarity of adjacent wild-type cells, with the effect sometimes spreading over a few cell diameters.

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Tissir, F., Goffinet, A. Shaping the nervous system: role of the core planar cell polarity genes. Nat Rev Neurosci 14, 525–535 (2013). https://doi.org/10.1038/nrn3525

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