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Planar cell polarity genes, Celsr1-3, in neural development

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Abstract

flamingo is among the ‘core’ planar cell-polarity genes, protein of which belongs to a unique cadherin subfamily. In contrast to the classic cadherins, composed of several extracellular cadherin repeats, one transmembrane domain and one cytoplasmic segment linked to catenin binding, Drosophila Flamingo has seven transmembrane segments and a cytoplasmic tail with no catenin-binding sequence. In Drosophila, Flamingo has pleotropic roles in controlling epithelial polarity and neuronal morphogenesis. Three mammalian orthologs of flamingo, Celsr1-3, are widely expressed in the nervous system. Recent work has shown that Celsr1-3 play important roles in neural development, such as in axon guidance, neuronal migration, and cilium polarity. Celsr1-3 single-gene knockout mice exhibit different phenotypes, but there are cooperative interactions among these genes.

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References

  1. Formstone CJ. 7TM-Cadherins: developmental roles and future challenges. Adv Exp Med Biol 2010, 706: 14–36.

    Article  PubMed  Google Scholar 

  2. Gray RS, Roszko I, Solnica-Krezel L. Planar cell polarity: coordinating morphogenetic cell behaviors with embryonic polarity. Dev Cell 2011, 21: 120–133.

    Article  PubMed  CAS  Google Scholar 

  3. Seifert JR, Mlodzik M. Frizzled/PCP signalling: a conserved mechanism regulating cell polarity and directed motility. Nat Rev Genet 2007, 8: 126–138.

    Article  PubMed  CAS  Google Scholar 

  4. Tissir F, Goffinet AM. Planar cell polarity signaling in neural development. Curr Opin Neurobiol 2010, 20: 572–577.

    Article  PubMed  CAS  Google Scholar 

  5. Wu J, Mlodzik M. A quest for the mechanism regulating global planar cell polarity of tissues. Trends Cell Biol 2009, 19: 295–305.

    Article  PubMed  Google Scholar 

  6. Gao FB, Kohwi M, Brenman JE, Jan LY, Jan YN. Control of dendritic field formation in Drosophila: the roles of Flamingo and competition between homologous neurons. Neuron 2000, 28: 91–101.

    Article  PubMed  CAS  Google Scholar 

  7. Steinel MC, Whitington PM. The atypical cadherin Flamingo is required for sensory axon advance beyond intermediate target cells. Dev Biol 2009, 327: 447–457.

    Article  PubMed  CAS  Google Scholar 

  8. Berger-Muller S, Suzuki T. Seven-pass transmembrane cadherins: roles and emerging mechanisms in axonal and dendritic patterning. Mol Neurobiol 2011, 44: 313–320.

    Article  PubMed  Google Scholar 

  9. Jones C, Chen P. Planar cell polarity signaling in vertebrates. Bioessays 2007, 29: 120–132.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  11. Zallen JA. Planar polarity and tissue morphogenesis. Cell 2007, 129: 1051–1063.

    Article  PubMed  CAS  Google Scholar 

  12. Amonlirdviman K, Khare NA, Tree DR, Chen WS, Axelrod JD, Tomlin CJ. Mathematical modeling of planar cell polarity to understand domineering nonautonomy. Science 2005, 307: 423–426.

    Article  PubMed  CAS  Google Scholar 

  13. Chen WS, Antic D, Matis M, Logan CY, Povelones M, Anderson GA, et al. Asymmetric homotypic interactions of the atypical cadherin flamingo mediate intercellular polarity signaling. Cell 2008, 133: 1093–1105.

    Article  PubMed  CAS  Google Scholar 

  14. Strutt H, Strutt D. Asymmetric localisation of planar polarity proteins: Mechanisms and consequences. Semin Cell Dev Biol 2009, 20: 957–963.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  16. Lee H, Adler PN. The function of the frizzled pathway in the Drosophila wing is dependent on inturned and fuzzy. Genetics 2002, 160: 1535–1547.

    PubMed  CAS  Google Scholar 

  17. Tio M, Ma C, Moses K. Extracellular regulators and pattern formation in the developing Drosophila retina. Biochem Soc Symp 1996, 62: 61–75.

    PubMed  CAS  Google Scholar 

  18. Strutt D, Johnson R, Cooper K, Bray S. Asymmetric localization of frizzled and the determination of notch-dependent cell fate in the Drosophila eye. Curr Biol 2002, 12: 813–824.

    Article  PubMed  CAS  Google Scholar 

  19. Das G, Reynolds-Kenneally J, Mlodzik M. The atypical cadherin Flamingo links Frizzled and Notch signaling in planar polarity establishment in the Drosophila eye. Dev Cell 2002, 2: 655–666.

    Article  PubMed  CAS  Google Scholar 

  20. Adler PN. Planar signaling and morphogenesis in Drosophila. Dev Cell 2002, 2: 525–535.

    Article  PubMed  CAS  Google Scholar 

  21. Weber U, Pataki C, Mihaly J, Mlodzik M. Combinatorial signaling by the Frizzled/PCP and Egfr pathways during planar cell polarity establishment in the Drosophila eye. Dev Biol 2008, 316: 110–123.

    Article  PubMed  CAS  Google Scholar 

  22. Sweeney NT, Li W, Gao FB. Genetic manipulation of single neurons in vivo reveals specific roles of flamingo in neuronal morphogenesis. Dev Biol 2002, 247: 76–88.

    Article  PubMed  CAS  Google Scholar 

  23. 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 2006, 119: 1118–1129.

    Article  PubMed  CAS  Google Scholar 

  24. Reuter JE, Nardine TM, Penton A, Billuart P, Scott EK, Usui T, et al. A mosaic genetic screen for genes necessary for Drosophila mushroom body neuronal morphogenesis. Development 2003, 130: 1203–1213.

    Article  PubMed  CAS  Google Scholar 

  25. Hakeda-Suzuki S, Berger-Muller S, Tomasi T, Usui T, Horiuchi SY, Uemura T, et al. Golden Goal collaborates with Flamingo in conferring synaptic-layer specificity in the visual system. Nat Neurosci, 14: 314–323.

  26. Lee RC, Clandinin TR, Lee CH, Chen PL, Meinertzhagen IA, Zipursky SL. The protocadherin Flamingo is required for axon target selection in the Drosophila visual system. Nat Neurosci 2003, 6: 557–563.

    Article  PubMed  CAS  Google Scholar 

  27. Senti KA, Usui T, Boucke K, Greber U, Uemura T, Dickson BJ. Flamingo regulates R8 axon-axon and axon-target interactions in the Drosophila visual system. Curr Biol 2003, 13: 828–832.

    Article  PubMed  CAS  Google Scholar 

  28. Chen PL, Clandinin TR. The cadherin Flamingo mediates leveldependent interactions that guide photoreceptor target choice in Drosophila. Neuron 2008, 58: 26–33.

    Article  PubMed  CAS  Google Scholar 

  29. Bao H, Berlanga ML, Xue M, Hapip SM, Daniels RW, Mendenhall JM, et al. The atypical cadherin flamingo regulates synaptogenesis and helps prevent axonal and synaptic degeneration in Drosophila. Mol Cell Neurosci 2007, 34: 662–678.

    Article  PubMed  CAS  Google Scholar 

  30. Shima Y, Copeland NG, Gilbert DJ, Jenkins NA, Chisaka O, Takeichi M, et al. Differential expression of the seven-pass transmembrane cadherin genes Celsr1-3 and distribution of the Celsr2 protein during mouse development. Dev Dyn 2002, 223: 321–332.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  32. Curtin JA, Quint E, Tsipouri V, Arkell RM, Cattanach B, Copp AJ, et al. Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. Curr Biol 2003, 13: 1129–1133.

    Article  PubMed  CAS  Google Scholar 

  33. Kibar Z, Vogan KJ, Groulx N, Justice MJ, Underhill DA, Gros P. Ltap, a mammalian homolog of Drosophila Strabismus/Van Gogh, is altered in the mouse neural tube mutant Loop-tail. Nat Genet 2001, 28: 251–255.

    Article  PubMed  CAS  Google Scholar 

  34. Wang J, Hamblet NS, Mark S, Dickinson ME, Brinkman BC, Segil N, et al. Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation. Development 2006, 133: 1767–1778.

    Article  PubMed  CAS  Google Scholar 

  35. 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 2006, 26: 2147–2156.

    Article  PubMed  CAS  Google Scholar 

  36. Ybot-Gonzalez P, Savery D, Gerrelli D, Signore M, Mitchell CE, Faux CH, et al. Convergent extension, planar-cell-polarity signalling and initiation of mouse neural tube closure. Development 2007, 134: 789–799.

    Article  PubMed  CAS  Google Scholar 

  37. 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 2004, 7: 205–216.

    Article  PubMed  CAS  Google Scholar 

  38. Tissir F, Bar I, Jossin Y, De Backer O, Goffinet AM. Protocadherin Celsr3 is crucial in axonal tract development. Nat Neurosci 2005, 8: 451–457.

    PubMed  CAS  Google Scholar 

  39. Wang Y, Thekdi N, Smallwood PM, Macke JP, Nathans J. Frizzled-3 is required for the development of major fiber tracts in the rostral CNS. J Neurosci 2002, 22: 8563–8573.

    PubMed  CAS  Google Scholar 

  40. Lyuksyutova AI, Lu CC, Milanesio N, King LA, Guo N, Wang Y, et al. Anterior-posterior guidance of commissural axons by Wnt-Frizzled signaling. Science 2003, 302: 1984–1988.

    Article  PubMed  CAS  Google Scholar 

  41. Price DJ, Kennedy H, Dehay C, Zhou L, Mercier M, Jossin Y, et al. The development of cortical connections. Eur J Neurosci 2006, 23: 910–920.

    Article  PubMed  Google Scholar 

  42. 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 2011, 20: 177–191.

    Article  PubMed  CAS  Google Scholar 

  43. Tissir F, Goffinet AM. Expression of planar cell polarity genes during development of the mouse CNS. Eur J Neurosci 2006, 23: 597–607.

    Article  PubMed  Google Scholar 

  44. Zhou L, Bar I, Achouri Y, Campbell K, De Backer O, Hebert JM, et al. Early forebrain wiring: genetic dissection using conditional Celsr3 mutant mice. Science 2008, 320: 946–949.

    Article  PubMed  CAS  Google Scholar 

  45. Zhou L, Gall D, Qu Y, Prigogine C, Cheron G, Tissir F, et al. Maturation of “neocortex isole” in vivo in mice. J Neurosci 2010, 30: 7928–7939.

    Article  PubMed  CAS  Google Scholar 

  46. Zhou L, Qu Y, Tissir F, Goffinet AM. Role of the atypical cadherin Celsr3 during development of the internal capsule. Cereb Cortex 2009, 19(Suppl 1): i114–119.

    Article  PubMed  Google Scholar 

  47. Fenstermaker AG, Prasad AA, Bechara A, Adolfs Y, Tissir F, Goffinet A, et al. Wnt/planar cell polarity signaling controls the anterior-posterior organization of monoaminergic axons in the brainstem. J Neurosci 2010, 30: 16053–16064.

    Article  PubMed  CAS  Google Scholar 

  48. Shima Y, Kawaguchi SY, Kosaka K, Nakayama M, Hoshino M, Nabeshima Y, et al. Opposing roles in neurite growth control by two seven-pass transmembrane cadherins. Nat Neurosci 2007, 10: 963–969.

    Article  PubMed  CAS  Google Scholar 

  49. Qu Y, Glasco DM, Zhou L, Sawant A, Ravni A, Fritzsch B, et al. Atypical cadherins Celsr1-3 differentially regulate migration of facial branchiomotor neurons in mice. J Neurosci 2010, 30: 9392–9401.

    Article  PubMed  CAS  Google Scholar 

  50. Tissir F, Qu Y, Montcouquiol M, Zhou L, Komatsu K, Shi D, et al. Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus. Nat Neurosci 2010, 13: 700–707.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Joint Laboratory for Brain Function and Health, Jinan University and The University of Hong Kong, Medical School of Jinan University, Guangzhou, 510632, China

    Jia Feng, Qi Han & Libing Zhou

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  1. Jia Feng
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  2. Qi Han
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Correspondence to Libing Zhou.

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Feng, J., Han, Q. & Zhou, L. Planar cell polarity genes, Celsr1-3, in neural development. Neurosci. Bull. 28, 309–315 (2012). https://doi.org/10.1007/s12264-012-1232-8

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  • DOI: https://doi.org/10.1007/s12264-012-1232-8

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