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Planar cell polarity: one or two pathways?

Abstract

In multicellular organisms, cells are polarized in the plane of the epithelial sheet, revealed in some cell types by oriented hairs or cilia. Many of the underlying genes have been identified in Drosophila melanogaster and are conserved in vertebrates. Here we dissect the logic of planar cell polarity (PCP). We review studies of genetic mosaics in adult flies — marked cells of different genotypes help us to understand how polarizing information is generated and how it passes from one cell to another. We argue that the prevailing opinion that planar polarity depends on a single genetic pathway is wrong and conclude that there are (at least) two independently acting processes. This conclusion has major consequences for the PCP field.

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Figure 1: Planar cell polarity in the Drosophila melanogaster pleura.
Figure 2: The functional assay.
Figure 3: A repolarizing clone in a stan fly.
Figure 4: Cuticle from the dorsal abdomen of Drosophila melanogaster.
Figure 5: The localization of planar cell polarity (PCP) proteins in clones in the wing.
Figure 6: Two Alternative models of planar cell polarity (PCP).

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References

  1. Brenner, S. My Life in Science (BioMed Central, London, 2001).

    Google Scholar 

  2. Drubin, D. Cell Polarity (eds Hames, B. & Glover, D.) (Oxford Univ. Press, Oxford, 2000).

    Google Scholar 

  3. Gho, M. & Schweisguth, F. Frizzled signalling controls orientation of asymmetric sense organ precursor cell divisions in Drosophila. Nature 393, 178–181 (1998).

    Article  CAS  PubMed  Google Scholar 

  4. Lawrence, P. A. Development and determination of hairs and bristles in the milkweed bug, Oncopeltus fasciatus (Lygaeidae, Hemiptera). J. Cell Sci. 1, 475–498 (1966).

    CAS  PubMed  Google Scholar 

  5. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Morgan, T. H. Regeneration in Allolobophora fœtida. Arch . Entwicklungsmech . Organism. 5, 570–586 (1897).

    Google Scholar 

  7. Lecuit, T., Samanta, R. & Wieschaus, E. slam encodes a developmental regulator of polarized membrane growth during cleavage of the Drosophila embryo. Dev. Cell 2, 425–436 (2002).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Nübler-Jung, K., Bonitz, R. & Sonnenschein, M. Cell polarity during wound healing in an insect epidermis. Development 100, 163–170 (1987).

    PubMed  Google Scholar 

  10. Seifert, J. R. & Mlodzik, M. Frizzled/PCP signalling: a conserved mechanism regulating cell polarity and directed motility. Nature Rev. Genet. 8, 126–138 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Strutt, D. Frizzled signalling and cell polarisation in Drosophila and vertebrates. Development 130, 4501–4513 (2003).

    Article  CAS  PubMed  Google Scholar 

  12. Fanto, M. & McNeill, H. Planar polarity from flies to vertebrates. J. Cell Sci. 117, 527–533 (2004).

    Article  CAS  PubMed  Google Scholar 

  13. Klein, T. J. & Mlodzik, M. Planar cell polarization: an emerging model points in the right direction. Annu. Rev. Cell Dev. Biol. 23, 23 (2005).

    Google Scholar 

  14. Wallingford, J. B. Planar cell polarity, ciliogenesis and neural tube defects. Hum. Mol. Genet. 15, R227–R234 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. 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 

  16. 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 

  17. Lewis, J. & Davies, A. Planar cell polarity in the inner ear: how do hair cells acquire their oriented structure? J. Neurobiol. 53, 190–201 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Zecca, M., Basler, K. & Struhl, G. Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing. Development 121, 2265–2278 (1995).

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  20. Kilian, B. et al. The role of Ppt/Wnt5 in regulating cell shape and movement during zebrafish gastrulation. Mech. Dev. 120, 467–476 (2003).

    Article  CAS  PubMed  Google Scholar 

  21. Nüsslein-Volhard, C. & Wieschaus, E. Mutations affecting segment number and polarity in Drosophila. Nature 287, 795–801 (1980).

    Article  PubMed  Google Scholar 

  22. Lewis, E. B. A gene complex controlling segmentation in Drosophila. Nature 276, 565–570 (1978).

    Article  CAS  PubMed  Google Scholar 

  23. Gubb, D. & Garcia-Bellido, A. A genetic analysis of the determination of cuticular polarity during development in Drosophila melanogaster. J. Embryol. Exp. Morphol. 68, 37–57 (1982).

    CAS  PubMed  Google Scholar 

  24. 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 

  25. Lawrence, P. A., Casal, J. & Struhl, G. Cell interactions and planar polarity in the abdominal epidermis of Drosophila. Development 131, 4651–4664 (2004).

    Article  CAS  PubMed  Google Scholar 

  26. Adler, P. N., Krasnow, R. E. & Liu, J. Tissue polarity points from cells that have higher Frizzled levels towards cells that have lower Frizzled levels. Curr. Biol. 7, 940–949 (1997).

    Article  CAS  PubMed  Google Scholar 

  27. Karner, C., Wharton, K. A. Jr & Carroll, T. J. Planar cell polarity and vertebrate organogenesis. Semin. Cell Dev. Biol. 17, 194–203 (2006).

    Article  PubMed  Google Scholar 

  28. Ma, D., Yang, C. H., McNeill, H., Simon, M. A. & Axelrod, J. D. Fidelity in planar cell polarity signalling. Nature 421, 543–547 (2003).

    CAS  PubMed  Google Scholar 

  29. Yang, C., Axelrod, J. D. & Simon, M. A. Regulation of Frizzled by Fat-like cadherins during planar polarity signaling in the Drosophila compound eye. Cell 108, 675–688 (2002).

    Article  CAS  PubMed  Google Scholar 

  30. 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 

  31. Deans, M. R. et al. Asymmetric distribution of Prickle-like 2 reveals an early underlying polarization of vestibular sensory epithelia in the inner ear. J. Neurosci. 27, 3139–3147 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. 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 

  33. Adler, P. N., Charlton, J. & Liu, J. Mutations in the cadherin superfamily member gene dachsous cause a tissue polarity phenotype by altering frizzled signaling. Development 125, 959–968 (1998).

    CAS  PubMed  Google Scholar 

  34. Casal, J., Struhl, G. & Lawrence, P. A. Developmental compartments and planar polarity in Drosophila. Curr. Biol. 12, 1189–1198 (2002).

    Article  CAS  PubMed  Google Scholar 

  35. Clark, H. F. et al. Dachsous encodes a member of the cadherin superfamily that controls imaginal disc morphogenesis in Drosophila. Genes Dev. 9, 1530–1542 (1995).

    Article  CAS  PubMed  Google Scholar 

  36. Zeidler, M. P., Perrimon, N. & Strutt, D. I. The four-jointed gene is required in the Drosophila eye for ommatidial polarity specification. Curr. Biol. 9, 1363–1372 (1999).

    Article  CAS  PubMed  Google Scholar 

  37. Zeidler, M. P., Perrimon, N. & Strutt, D. I. Multiple roles for four-jointed in planar polarity and limb patterning. Dev. Biol. 228, 181–196 (2000).

    Article  CAS  PubMed  Google Scholar 

  38. Simon, M. A. Planar cell polarity in the Drosophila eye is directed by graded Four-jointed and Dachsous expression. Development 131, 6175–6184 (2004).

    Article  CAS  PubMed  Google Scholar 

  39. 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 

  40. Strutt, H. & Strutt, D. Nonautonomous planar polarity patterning in Drosophila: Dishevelled-independent functions of frizzled. Dev. Cell 3, 851–863 (2002).

    Article  CAS  PubMed  Google Scholar 

  41. Matakatsu, H. & Blair, S. S. Interactions between Fat and Dachsous and the regulation of planar cell polarity in the Drosophila wing. Development 131, 3785–3794 (2004).

    Article  CAS  PubMed  Google Scholar 

  42. Matakatsu, H. & Blair, S. S. Separating the adhesive and signaling functions of the Fat and Dachsous protocadherins. Development 133, 2315–2324 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Usui, T. et al. Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled. Cell 98, 585–595. (1999).

    Article  CAS  PubMed  Google Scholar 

  44. Strutt, D. & Strutt, H. Differential activities of the core planar polarity proteins during Drosophila wing patterning. Dev. Biol. 302, 181–194 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  46. Tree, D. R. et al. Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling. Cell 109, 371–381 (2002).

    Article  CAS  PubMed  Google Scholar 

  47. Axelrod, J. D. Unipolar membrane association of Dishevelled mediates Frizzled planar cell polarity signaling. Genes Dev. 15, 1182–1187 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Strutt, D. I. Asymmetric localization of Frizzled and the establishment of cell polarity in the Drosophila wing. Mol. Cell 7, 367–375 (2001).

    Article  CAS  PubMed  Google Scholar 

  49. Strutt, D. I. The asymmetric subcellular localisation of components of the planar polarity pathway. Semin. Cell Dev. Biol. 13, 225–231 (2002).

    Article  CAS  PubMed  Google Scholar 

  50. Bastock, R., Strutt, H. & Strutt, D. Strabismus is asymmetrically localised and binds to Prickle and Dishevelled during Drosophila planar polarity patterning. Development 130, 3007–3014 (2003).

    Article  CAS  PubMed  Google Scholar 

  51. Adler, P. N., Taylor, J. & Charlton, J. The domineering non-autonomy of Frizzled and Van Gogh clones in the Drosophila wing is a consequence of a disruption in local signaling. Mech. Dev. 96, 197–207 (2000).

    Article  CAS  PubMed  Google Scholar 

  52. Rock, R., Schrauth, S. & Gessler, M. Expression of mouse Dchs1, Fjx1, and Fat-j suggests conservation of the planar cell polarity pathway identified in Drosophila. Dev. Dyn. 234, 747–755 (2005).

    Article  CAS  PubMed  Google Scholar 

  53. Day, S. J. & Lawrence, P. A. Measuring dimensions: the regulation of size and shape. Development 127, 2977–2987 (2000).

    CAS  PubMed  Google Scholar 

  54. Lawrence, P. A. Last hideout of the unknown? Nature 429, 247 (2004).

    Article  CAS  PubMed  Google Scholar 

  55. Cho, E. et al. Delineation of a Fat tumor suppressor pathway. Nature Genet. 38, 1142–1150 (2006).

    Article  CAS  PubMed  Google Scholar 

  56. Bennett, F. C. & Harvey, K. F. Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway. Curr. Biol. 16, 2101–2110 (2006).

    Article  CAS  PubMed  Google Scholar 

  57. Silva, E., Tsatskis, Y., Gardano, L., Tapon, N. & McNeill, H. The tumor-suppressor gene fat controls tissue growth upstream of expanded in the Hippo signaling pathway. Curr. Biol. 16, 2081–2089 (2006).

    Article  CAS  PubMed  Google Scholar 

  58. Willecke, M. et al. The Fat cadherin acts through the Hippo tumor-suppressor pathway to regulate tissue size. Curr. Biol. 16, 2090–2100 (2006).

    Article  CAS  PubMed  Google Scholar 

  59. Villano, J. L. & Katz, F. N. four-jointed is required for intermediate growth in the proximal–distal axis in Drosophila. Development 121, 2767–2777 (1995).

    CAS  PubMed  Google Scholar 

  60. Brodsky, M. H. & Steller, H. Positional information along the dorsal–ventral axis of the Drosophila eye: graded expression of the four-jointed gene. Dev. Biol. 173, 428–446 (1996).

    Article  CAS  PubMed  Google Scholar 

  61. Strutt, H., Mundy, J., Hofstra, K. & Strutt, D. Cleavage and secretion is not required for Four-jointed function in Drosophila patterning. Development 131, 881–890 (2004).

    Article  CAS  PubMed  Google Scholar 

  62. Ashery-Padan, R., Alvarez-Bolado, G., Klamt, B., Gessler, M. & Gruss, P. Fjx1, the murine homologue of the Drosophila four-jointed gene, codes for a putative secreted protein expressed in restricted domains of the developing and adult brain. Mech. Dev. 80, 213–217 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Mahoney, P. A. et al. The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily. Cell 67, 853–868 (1991).

    Article  CAS  PubMed  Google Scholar 

  64. Rawls, A. S., Guinto, J. B. & Wolff, T. The cadherins Fat and Dachsous regulate dorsal/ventral signaling in the Drosophila eye. Curr. Biol. 12, 1021–1026 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. 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 

  66. 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).

    Article  CAS  PubMed  Google Scholar 

  67. Vinson, C. R., Conover, S. & Adler, P. N. A Drosophila tissue polarity locus encodes a protein containing seven potential transmembrane domains. Nature 338, 263–264 (1989).

    Article  CAS  PubMed  Google Scholar 

  68. 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 

  69. 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 

  70. Montcouquiol, M. et al. Asymmetric localization of VANGL2 and FZ3 indicate novel mechanisms for planar cell polarity in mammals. J. Neurosci. 26, 5265–5275 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Gubb, D. et al. The balance between isoforms of the Prickle LIM domain protein is critical for planar polarity in Drosophila imaginal discs. Genes Dev. 13, 2315–2327 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Katoh, M. & Katoh, M. Identification and characterization of human PRICKLE1 and PRICKLE2 genes as well as mouse Prickle1 and Prickle2 genes homologous to Drosophila tissue polarity gene prickle. Int. J. Mol. Med. 11, 249–256 (2003).

    CAS  PubMed  Google Scholar 

  73. Bekman, E. & Henrique, D. Embryonic expression of three mouse genes with homology to the Drosophila melanogaster prickle gene. Mech. Dev. 119, S77–S81 (2002).

    Article  PubMed  Google Scholar 

  74. Theisen, H. et al. dishevelled is required during Wingless signaling to establish both cell polarity and cell identity. Development 120, 347–360 (1994).

    CAS  PubMed  Google Scholar 

  75. Klingensmith, J., Nusse, R. & Perrimon, N. The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the Wingless signal. Genes Dev. 8, 118–130 (1994).

    Article  CAS  PubMed  Google Scholar 

  76. 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 

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Acknowledgements

We thank the Wellcome Trust and the Medical Research Council, UK, for support and D. Strutt for advice and encouragement. G.S. is a Howard Hughes Medical Institute Investigator.

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Correspondence to Peter A. Lawrence.

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Glossary

Clones

Patches of clonally derived cells in an organism that have been engineered to be genetically distinct from surrounding cells (for example, a homozygous mutant clone in a heterozygous background).

Convergent extension

The process by which a sheet of cells changes shape by extending in one direction and narrowing — converging — in a direction at right angles to the extension.

Ommatidia

The elements of the compound eye of insects (in Drosophila melanogaster, the eye is formed from 800 ommatidia), each of which is an independent visual unit that contains eight photoreceptor cells, surrounded by four cone cells that secrete the lens, and seven pigment cells.

Stereocilium

A large, rigid, actin-filled microvillus on the apical surface of hair cells in the inner ear.

Tergites

Cuticular plates, one per segment, that bear oriented hairs and bristles that make up most of the dorsal abdomen of Drosophila melanogaster and other insects.

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Lawrence, P., Struhl, G. & Casal, J. Planar cell polarity: one or two pathways?. Nat Rev Genet 8, 555–563 (2007). https://doi.org/10.1038/nrg2125

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