Latrophilin Signalling in Tissue Polarity and Morphogenesis

  • Tobias Langenhan
  • Andreas P. Russ
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 706)


Understanding the mechanisms that coordinate the polarity of cells and tissues during embryogenesis and morphogenesis is a fundamental problem in developmental biology. We have recently demonstrated that the putative neurotoxin receptor lat-1 defines a mechanism required for the alignment of cell division planes in the early embryo of the nematode C. elegans. Our analysis suggests that lat-1 is required for the propagation rather than the initial establishment of polarity signals. Similar to the role of the flamingo/CELSR protein family in the control of planar cell polarity, these results implicate an evolutionary conserved subfamily of adhesion-GPCRs in the control of tissue polarity and morphogenesis.


Polarize Signal Planar Cell Polarity Asymmetric Cell Division Online Review Division Plane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Gönczy P. Mechanisms of asymmetric cell division: flies and worms pave the way. Nat Rev Mol Cell Biol 2008; 9(5):355–366.PubMedCrossRefGoogle Scholar
  2. 2.
    Siller KH, Doe CQ. Spindle orientation during asymmetric cell division. Nat Cell Biol 2009; 11(4):365–374.PubMedCrossRefGoogle Scholar
  3. 3.
    Zallen JA. Planar polarity and tissue morphogenesis. Cell 2007; 129(6):1051–1063.PubMedCrossRefGoogle Scholar
  4. 4.
    Townes, Holtfreter J. Directed movements and selective adhesion of embryonic amphibian cells J Exp Zool 1955; 128(1):53–120.CrossRefGoogle Scholar
  5. 5.
    Tepass U, Godt D, Winklbauer R. Cell sorting in animal development: signalling and adhesive mechanisms in the formation of tissue boundaries. Curr Opin Genet Dev 2002; 12(5):572–582.PubMedCrossRefGoogle Scholar
  6. 6.
    Steinberg MS. Differential adhesion in morphogenesis: a modern view. Curr Opin Genet Dev 2007; 17(4):281–286.PubMedCrossRefGoogle Scholar
  7. 7.
    Halbleib JM, Nelson WJ. Cadherins in development: cell adhesion, sorting and tissue morphogenesis. Genes Dev 2006; 20(23):3199–3214.PubMedCrossRefGoogle Scholar
  8. 8.
    Hinck L. The versatile roles of “axon guidance” cues in tissue morphogenesis. Dev Cell 2004; 7(6):783–793.PubMedCrossRefGoogle Scholar
  9. 9.
    Harmar AJ. Family-B G-protein-coupled receptors. Genome Biol 2001; 2(12):REVIEWS3013.Google Scholar
  10. 10.
    Bjarnadóttir, Fredriksson R, Schiöth. The adhesion-GPCRs: A unique family of G protein-coupled receptors with important roles in both central and peripheral tissues. Cell Mol Life Sci 2007.Google Scholar
  11. 11.
    Nordström K, Lagerström M, Wallér L et al. The Secretin GPCRs descended from the family of adhesion-GPCRs. Molecular Biology and Evolution 2008.Google Scholar
  12. 12.
    Veninga H, Becker S, Hoek RM et al. Analysis of CD97 expression and manipulation: antibody treatment but not gene targeting curtails granulocyte migration. J Immunol 2008; 181(9):6574–6583.PubMedGoogle Scholar
  13. 13.
    Kwakkenbos MJ, Kop EN, Matmati M et al. The EGF-TM7 family: a postgenomic view. Immunogenetics 2004; 55(10):655–666.PubMedCrossRefGoogle Scholar
  14. 14.
    Piao X, Hill RS, Bodell A et al. G protein-coupled receptor-dependent development of human frontal cortex. Science 2004; 303(5666):2033–2036.PubMedCrossRefGoogle Scholar
  15. 15.
    Usui T, Shima Y, Shimada Y et al. Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled. Cell 1999; 98(5):585–595.PubMedCrossRefGoogle Scholar
  16. 16.
    Chae J, Kim MJ, Goo JH et al. The Drosophila tissue polarity gene starry night encodes a member of the protocadherin family. Development 1999; 126(23):5421–5429.PubMedGoogle Scholar
  17. 17.
    Formstone CJ, Mason I. Combinatorial activity of Flamingo proteins directs convergence and extension within the early zebrafish embryo via the planar cell polarity pathway. Dev Biol 2005; 282(2):320–335.PubMedCrossRefGoogle Scholar
  18. 18.
    Lawrence PA, Strahl G, Casal J. Planar cell polarity: one or two pathways? Nat Rev Genet 2007; 8(7):555–563.PubMedCrossRefGoogle Scholar
  19. 19.
    Stratt D. The planar polarity pathway. Curr Biol 2008; 18(19):R898–R902.CrossRefGoogle Scholar
  20. 20.
    Shima Y, Kengaku M, Hirano T et al. Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin. Dev Cell 2004; 7(2):205–216.PubMedCrossRefGoogle Scholar
  21. 21.
    Curtin J, Quint E, Tsipouri V et al. Mutation of Celsrl disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. Curr Biol 2003; 13(13): 1129–1133.PubMedCrossRefGoogle Scholar
  22. 22.
    Shima Y, Kawaguchi Sy, Kosaka K et al. Opposing roles in neurite growth control by two seven-pass transmembrane cadherins. Nat Neurosci 2007; 10(8):963–969.PubMedCrossRefGoogle Scholar
  23. 23.
    Tissir F, Bar I, Jossin Y, De Backer O et al. Protocadherin Celsr3 is crucial in axonal tract development. Nat. Neurosci 2005; 8(4):451–457.PubMedGoogle Scholar
  24. 24.
    Krasnoperov VG, Bittner MA, Beavis R et al. Alpha-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor. Neuron 1997; 18(6):925–937.PubMedCrossRefGoogle Scholar
  25. 25.
    Krasnoperov VG, Beavis R, Chepurny OG et al. The calcium-independent receptor of alpha-latrotoxin is not a neurexin. Biochem Biophys Res Commun 1996; 227(3):868–875.PubMedCrossRefGoogle Scholar
  26. 26.
    Südhof TC. Alpha-Latrotoxin and its receptors: neurexins and CIRL/latrophilins. Annu Rev Neurosci 2001; 24:933–962.PubMedCrossRefGoogle Scholar
  27. 27.
    Capogna M, Volynski KE, Emptage NJ et al. The alpha-latrotoxin mutant LTXN4C enhances spontaneous and evoked transmitter release in CA3 pyramidal neurons. J Neurosci 2003; 23(10):4044–4053.PubMedGoogle Scholar
  28. 28.
    Willson J, Amliwala K, Davis A et al. Latrotoxin receptor signaling engages the UNC-13-dependent vesicle-priming pathway in C. elegans. Curr Biol 2004; 14(15):1374–1379.PubMedCrossRefGoogle Scholar
  29. 29.
    Langenhan T, Prömel S, Mestek L et al. Latrophilin signalling links anterior-posterior tissue polarity and oriented cell divisions in the C. elegans embryo. Dev Cell 2009; 17:494–504.PubMedCrossRefGoogle Scholar
  30. 30.
    Mee CJ, Tomlinson SR, Perestenko PV et al. Latrophilin is required for toxicity of black widow spider venom in Caenorhabditis elegans. Biochem J 2004; 378(Pt 1): 185–191.PubMedCrossRefGoogle Scholar
  31. 31.
    Hutter H, Vogel BE, Plenefisch JD et al. Conservation and novelty in the evolution of cell adhesion and extracellular matrix genes. Science 2000; 287(5455):989–994.PubMedCrossRefGoogle Scholar
  32. 32.
    Pettitt J. The cadherin superfamily. WormBook: the online review of C elegans biology 2005:1–9.Google Scholar
  33. 33.
    Lin YJ, Seroude L, Benzer S. Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 1998; 282(5390):943–946.PubMedCrossRefGoogle Scholar
  34. 34.
    Sulston JE, Schierenberg E, White JG et al. The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol 1983; 100(1):64–119.PubMedCrossRefGoogle Scholar
  35. 35.
    Gönczy P, Rose LS. Asymmetric cell division and axis formation in the embryo. WormBook: the online review of C elegans biology 2005:1–20.Google Scholar
  36. 36.
    Priess JR. Notch signaling in the C. elegans embryo. WormBook: the online review of C elegans biology 2005:1–16.Google Scholar
  37. 37.
    Schnabel R. Why does a nematode have an invariant cell lineage? Seminars in Cell and Developmental Biology 1997; 8(4):341–349.PubMedCrossRefGoogle Scholar
  38. 38.
    Kaletta T, Schnabel H, Schnabel R. Binary specification of the embryonic lineage in Caenorhabditis elegans. Nature 1997; 390(6657):294–298.PubMedCrossRefGoogle Scholar
  39. 39.
    Lin R, Hill RJ, Priess JR. POP-1 and anterior-posterior fate decisions in C. elegans embryos. Cell 1998; 92(2):229–239.PubMedCrossRefGoogle Scholar
  40. 40.
    Mizumoto K, Sawa H. Two betas or not two betas: regulation of asymmetric division by beta-catenin. Trends Cell Biol 2007; 17(10):465–473.PubMedCrossRefGoogle Scholar
  41. 41.
    Walston TD, Hardin J. Wnt-dependent spindle polarization in the early C. elegans embryo. Seminars in Cell and Developmental Biology 2006; 17(2):204–213.PubMedCrossRefGoogle Scholar
  42. 42.
    Cowan CR, Hyman AA. Asymmetric cell division in C. elegans: cortical polarity and spindle positioning. Annu Rev Cell Dev Biol 2004; 20:427–453.PubMedCrossRefGoogle Scholar
  43. 43.
    Hutter H, Schnabel R. Specification of anterior-posterior differences within the AB lineage in the C. elegans embryo: a polarising induction. Development 1995; 121(5):1559–1568.PubMedGoogle Scholar
  44. 44.
    Goldstein B. Cell contacts orient some cell division axes in the Caenorhabditis elegans embryo. J Cell Biol 1995; 129(4):1071–1080.PubMedCrossRefGoogle Scholar
  45. 45.
    Goldstein B, Takeshita H, Mizumoto K et al. Wnt signals can function as positional cues in establishing cell polarity. Dev Cell 2006; 10(3):391–396.PubMedCrossRefGoogle Scholar
  46. 46.
    Rocheleau CE, Downs WD, Lin R et al. Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. Cell 1997; 90(4):707–716.PubMedCrossRefGoogle Scholar
  47. 47.
    Schlesinger A, Shelton CA, Maloof JN et al. Wnt pathway components orient a mitotic spindle in the early Caenorhabditis elegans embryo without requiring gene transcription in the responding cell. Genes Dev 1999; 13(15):2028–2038.PubMedCrossRefGoogle Scholar
  48. 48.
    Thorpe CJ, Schlesinger A, Carter JC et al. Wnt signaling polarizes an early C. elegans blastomere to distinguish endoderm from mesoderm. Cell 1997; 90(4):695–705.PubMedCrossRefGoogle Scholar
  49. 49.
    Walston T, Tuskey C, Edgar L et al. Multiple Wnt signaling pathways converge to orient the mitotic spindle in early C. elegans embryos. Dev Cell 2004; 7(6):831–841.PubMedCrossRefGoogle Scholar
  50. 50.
    Bei Y, Hogan J, Berkowitz LA et al. SRC-1 and Wnt signaling act together to specify endoderm and to control cleavage orientation in early C. elegans embryos. Dev Cell 2002; 3(1):113–125.PubMedCrossRefGoogle Scholar
  51. 51.
    Bischoff M, Schnabel R. A posterior centre establishes and maintains polarity of the Caenorhabditis elegans embryo by a Wnt-dependent relay mechanism. PLoS Biol 2006; 4(12):e396.PubMedCrossRefGoogle Scholar
  52. 52.
    Park FD, Tenlen JR, Priess JR. C. elegans MOM-5/frizzled functions in MOM-2/Wnt-independent cell polarity and is localized asymmetrically prior to cell division. Curr Biol 2004; 14(24):2252–2258.PubMedCrossRefGoogle Scholar
  53. 53.
    Park FD, Priess JR. Establishment of POP-1 asymmetry in early C. elegans embryos. Development 2003; 130(15):3547–3556.PubMedCrossRefGoogle Scholar
  54. 54.
    Green JL, Inoue T, Sternberg PW. Opposing Wnt pathways orient cell polarity during organogenesis. Cell 2008; 134(4):646–656.PubMedCrossRefGoogle Scholar
  55. 55.
    Lin H-H, Chang G-W, Davies JQ et al. Autocatalytic cleavage of the EMR2 receptor occurs at a conserved G protein-coupled receptor proteolytic site motif. J Biol Chem 2004; 279(30):31823–31832.PubMedCrossRefGoogle Scholar
  56. 56.
    Vakonakis I, Langenhan T, Prömel S et al. Solution structure and sugar-binding mechanism of mouse latrophilin-1 RBL: a 7TM receptor-attached lectin-like domain. Structure 2008; 16(6):944–953.PubMedCrossRefGoogle Scholar
  57. 57.
    Steinel MC, Whitington PM. The atypical cadherin Flamingo is required for sensory axon advance beyond intermediate target cells. Dev Biol 2009; 327(2):447–457.PubMedCrossRefGoogle Scholar
  58. 58.
    Davies B, Baumann C, Kirchhoff C et al. Targeted deletion of the epididymal receptor HE6 results in fluid dysregulation and male infertility. Mol Cell Biol 2004; 24(19):8642–8648.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Tobias Langenhan
    • 1
  • Andreas P. Russ
    • 2
  1. 1.Institute of PhysiologyUniversity of WürzburgWürzburgGermany
  2. 2.Department of BiochemistryUniversity of OxfordOxfordUK

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