Cadherins in Neural Development

  • Lewis L. Brayshaw
  • Stephen R. PriceEmail author


Cadherins play many diverse roles in the development of the nervous system of vertebrates. Far from being simple adhesion molecules, they also orchestrate cell generation, cell movements, and cell morphogenesis. Cadherins also regulate specificity of cell-to-cell interactions during neuronal circuit formation and function. Cadherin expression during neural development is also dynamic and highly regulated. At each phase of embryo development, cadherins emerge as key molecular determinants of neural function through their many diverse binding partners. Additionally, they play important roles in the plasticity of the nervous system, a key feature believed to underpin the ability of the brain to function. Many neurodevelopmental disorders also have cadherin disfunction at their heart indicating that cadherin-based therapies may emerge as future treatments for these devastating conditions.


Cadherin Neuron Progenitor cell Morphogenesis Synapse Mental disorders Dendrite Axon Nucleogenesis 


  1. Abe K, Chisaka O, Van Roy F, Takeichi M (2004) Stability of dendritic spines and synaptic contacts is controlled by alpha N-catenin. Nat Neurosci 7:357–363PubMedCrossRefGoogle Scholar
  2. Ahrens T, Pertz O, Haussinger D et al (2002) Analysis of heterophilic and homophilic interactions of cadherins using the c-Jun/c-Fos dimerization domains. J Biol Chem 277:19455–19460PubMedCrossRefGoogle Scholar
  3. Aiga M, Levinson JN, Bamji SX (2011) N-cadherin and neuroligins cooperate to regulate synapse formation in hippocampal cultures. J Biol Chem 286:851–858PubMedPubMedCentralCrossRefGoogle Scholar
  4. Alberini CM (2009) Transcription factors in long-term memory and synaptic plasticity. Physiol Rev 89:121–145PubMedCrossRefGoogle Scholar
  5. Andrews GL, Mastick GS (2003) R-cadherin is a Pax6-regulated, growth-promoting cue for pioneer axons. J Neurosci 23:9873–9880PubMedPubMedCentralGoogle Scholar
  6. Arikkath J, Reichardt LF (2008) Cadherins and catenins at synapses: roles in synaptogenesis and synaptic plasticity. Trends Neurosci 31:487–494PubMedPubMedCentralCrossRefGoogle Scholar
  7. Astick M, Tubby K, Mubarak WM et al (2014) Central topography of cranial motor nuclei controlled by differential cadherin expression. Curr Biol 24:2541–2547PubMedPubMedCentralCrossRefGoogle Scholar
  8. Babb SG, Marrs J (2004) E-cadherin regulates cell movements and tissue formation in early zebrafish embryos. Dev Dyn 230:263–277PubMedCrossRefGoogle Scholar
  9. Barnes SH, Price SR, Wentzel C, Guthrie SC (2010) Cadherin-7 and cadherin-6B differentially regulate the growth, branching and guidance of cranial motor axons. Development 137:805–814PubMedPubMedCentralCrossRefGoogle Scholar
  10. Bekirov IH, Nagy V, Svoronos A et al (2008) Cadherin-8 and N cadherin differentially regulate pre- and postsynaptic development of the hippocampal mossy fiber pathway. Hippocampus 18:349–363PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bellion A, Baudoin J-P, Alvarez C (2005) Nucleokinesis in tangentially migrating neurons comprises two alternating phases: forward migration of the Golgi/centrosome associated with centrosome splitting and myosin contraction at the rear. J Neurosci 25:5691–5699PubMedCrossRefGoogle Scholar
  12. Bello SM, Millo H, Rajebhosale M, Price SR (2012) Catenin-dependent cadherin function drives divisional segregation of spinal motor neurons. J Neurosci 32:490–505PubMedPubMedCentralCrossRefGoogle Scholar
  13. Bhalla K, LuoY BT et al (2008) Alterations in CDH15 and KIRREL3 in patients with mild to severe intellectual disability. Am J Hum Genet 83:703–713PubMedPubMedCentralCrossRefGoogle Scholar
  14. Bixby JL, Lilien J, Reichardt LF (1988) Identification of the major proteins that promote neuronal process outgrowth on Schwann cells in vitro. J Cell Biol 107:353–361PubMedCrossRefGoogle Scholar
  15. Bixby JL, Grunwald GB, Bookman RJ (1994) Ca2+ influx and neurite growth in response to purified N-cadherin and laminin. J Cell Biol 127:1461–1475PubMedCrossRefGoogle Scholar
  16. Bliss TV, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 232:331–356PubMedPubMedCentralCrossRefGoogle Scholar
  17. Borchers A, David R, Wedlich D (2001) Xenopus cadherin-11 restrains cranial neural crest migration and influences neural crest specification. Development 128:3049–3060PubMedGoogle Scholar
  18. Børglum AD, Demontis D, Grove J et al (2014) Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci. Mol Psychiatry 19:325–333PubMedPubMedCentralCrossRefGoogle Scholar
  19. Bozdagi O, Valcin M, Poskanzer K et al (2004) Temporally distinct demands for classic cadherins in synapse formation and maturation. Mol Cell Neurosci 27:509–521PubMedPubMedCentralCrossRefGoogle Scholar
  20. Bozdagi O, Wang XB, Nikitczuk JS et al (2010) Persistence of coordinated long-term potentiation and dendritic spine enlargement at mature hippocampal CA1 synapses requires N-cadherin. J Neurosci 30:9984–9989PubMedPubMedCentralCrossRefGoogle Scholar
  21. Bradke F, Dotti CG (2000) Establishment of neuronal polarity: lessons from cultured hippocampal neurons. Curr Opin Neurobiol 10:574–581PubMedCrossRefGoogle Scholar
  22. Brigidi GS, Bamji SX (2011) Cadherin-catenin adhesion complexes at the synapse. Curr Opin Neurobiol 21:208–214PubMedCrossRefGoogle Scholar
  23. Cappello S, Attardo A, Wu X et al (2006) The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface. Nat Neurosci 9:1099–1107. doi: 10.1038/nn1744 PubMedCrossRefGoogle Scholar
  24. Carver EA, Jiang R, Lan Y et al (2001) The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition the mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition. Mol Cell Biol 21:8184–8188. doi: 10.1128/MCB.21.23.8184 PubMedPubMedCentralCrossRefGoogle Scholar
  25. Chadborn N, Eickholt B, Doherty P, Bolsover S (2002) Direct measurement of local raised subplasmalemmal calcium concentrations in growth cones advancing on an N-cadherin substrate. Eur J Neurosci 15:1891–1898PubMedCrossRefGoogle Scholar
  26. Chang L, Blain D, Bertuzzi S, Brooks BP (2006) Uveal coloboma: clinical and basic science update. Curr Opin Ophthalmol 17:447–470. doi: 10.1097/ PubMedCrossRefGoogle Scholar
  27. Chapman NH, Estes A, Munson J et al (2011) Genome-scan for IQ discrepancy in au- tism: evidence for loci on chromosomes 10 and 16. Hum Genet 129:59–70PubMedPubMedCentralCrossRefGoogle Scholar
  28. Chen S, Lewis B, Moran A, Xie T (2012) Cadherin-mediated cell adhesion is critical for the closing of the mouse optic fissure. PloS One 7:1–8. doi: 10.1371/journal.pone.0051705 Google Scholar
  29. Chenn A, Walsh C (2003) Increased neuronal production, enlarged forebrains and cytoarchitectural distortions in beta-catenin overexpressing transgenic mice. Cereb Cortex 13:599–606. doi: 10.1093/cercor/13.6.599 PubMedCrossRefGoogle Scholar
  30. Chenn A, Zhang YA, Chang BT, McConnell SK (1998) Intrinsic polarity of mammalian neuroepithelial cells. Mol Cell Neurosci 11:183–193. doi: 10.1006/mcne.1998.0680 PubMedCrossRefGoogle Scholar
  31. Chow RL, Lang RA (2001) Early eye development in vertebrates. Annu Rev Cell Dev Biol 17:255–296PubMedCrossRefGoogle Scholar
  32. Chu TT, Liu Y (2010) An integrated genomic analysis of gene function correlation on schizophrenia susceptibility genes. J Hum Genet 55:285–292PubMedCrossRefGoogle Scholar
  33. Ciruna B, Rossant J (2001) FGF signalling regulates mesoderm cell Fate specification and morphogenetic movement at the primitive streak. Dev Cell 1:37–49. doi: 10.1016/S1534-5807(01)00017-X PubMedCrossRefGoogle Scholar
  34. Clay MR, Halloran MC (2014) Cadherin 6 promotes neural crest cell detachment via F-actin regulation and influences active Rho distribution during epithelial-to-mesenchymal transition. Development 141:2506–2515. doi: 10.1242/dev.105551 PubMedPubMedCentralCrossRefGoogle Scholar
  35. Coles EG, Taneyhill LA, Bronner-Fraser M (2007) A critical role for Cadherin6B in regulating avian neural crest emigration. Dev Biol 312:533–544. doi: 10.1016/j.ydbio.2007.09.056 PubMedPubMedCentralCrossRefGoogle Scholar
  36. Costa MR, Wen G, Lepier A et al (2008) Par-complex proteins promote proliferative progenitor divisions in the developing mouse cerebral cortex. Development 135:11–22. doi: 10.1242/dev.009951 PubMedCrossRefGoogle Scholar
  37. Crepel A, De Wolf V, Brison N et al (2014) Association of CDH11 with non-syndromic ASD. Am J Med Genet B Neuropsychiatr Genet 165:391–398CrossRefGoogle Scholar
  38. Dady A, Blavet C, Duband JL (2012) Timing and kinetics of E- to N-cadherin switch during neurulation in the avian embryo. Dev Dyn 241:1333–1349. doi: 10.1002/dvdy.23813 PubMedCrossRefGoogle Scholar
  39. Das RM, Storey KG (2014) Apical abscission alters cell polarity and dismantles the primary cilium during neurogenesis. Science 343:200–204. doi: 10.1126/science.1247521 PubMedPubMedCentralCrossRefGoogle Scholar
  40. de Anda FC, Pollarolo G, Da Silva JS et al (2005) Centrosome localization determines neuronal polarity. Nature 436:704–708PubMedCrossRefGoogle Scholar
  41. de Anda F, Gartner A, Tsai LH, Dotti CG (2008) Pyramidal neuron polarity axis is defined at the bipolar stage. J Cell Sci 121:178–185CrossRefGoogle Scholar
  42. de Anda FC, Meletis K, Ge X et al (2010) Centrosome motility is essential for initial axon formation in the neocortex. J Neurosci 30:10391–10406PubMedCrossRefGoogle Scholar
  43. Demireva EY, Shapiro LS, Jessell TM, Zampieri N (2011) Motor neuron position and topographic order imposed by β - and γ-catenin activities. Cell 147:641–52PubMedPubMedCentralCrossRefGoogle Scholar
  44. Doe CQ (2008) Neural stem cells: balancing self-renewal with differentiation. Development 135:1575–1587. doi: 10.1242/dev.014977 PubMedCrossRefGoogle Scholar
  45. Dotti CG, Sullivan CA, Banker GA (1988) The establishment of polarity by hippocampal neurons in culture. J Neurosci 8:1454–1468PubMedGoogle Scholar
  46. Duan X, Krishnaswamy A, De la Huerta I, Sanes JR (2014) Type II cadherins guide assembly of a direction-selective retinal circuit. Cell 158:793–807PubMedCrossRefGoogle Scholar
  47. Dunah AW, Hueske E, Wyszynski M (2005) LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses. Nat Neurosci 8:458–467PubMedGoogle Scholar
  48. Dupin E, Creuzet S, Le Douarin NM (2006) The contribution of the neural crest to the vertebrate body. Adv Exp Med Biol 589:96–119PubMedCrossRefGoogle Scholar
  49. Elia LP, Yamamoto M, Zang K, Reichardt LF (2006) p120 catenin regulates dendritic spine and synapse development through Rho-family GTPases and cadherins. Neuron 51:43–56PubMedPubMedCentralCrossRefGoogle Scholar
  50. Fannon AM, Colman DR (1996) A model for central synaptic junctional complex formation based on the differential adhesive specificities of the cadherins. Neuron 17:423–434PubMedCrossRefGoogle Scholar
  51. Farkas LM, Huttner WB (2008) The cell biology of neural stem and progenitor cells and its significance for their proliferation versus differentiation during mammalian brain development. Curr Opin Cell Biol 20:707–715. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  52. Gartner A, Fornasiero EF, Dotti CG (2012a) N-cadherin: a new player in neuronal polarity. Cell Cycle 11:2223–2224PubMedPubMedCentralCrossRefGoogle Scholar
  53. Gartner A, Fornasiero EF, Munck S et al (2012b) N-cadherin specifies first asymmetry in developing neurons. EMBO J 31:1893–1903PubMedPubMedCentralCrossRefGoogle Scholar
  54. Gärtner A, Fornasiero EF, Dotti CG (2014a) Cadherins as regulators of neuronal polarity. Cell Adh Migr 14:1–8Google Scholar
  55. Gärtner A, Fornasiero EF, Valtorta F, Dotti CG (2014b) Distinct temporal hierarchies in membrane and cytoskeleton dynamics precede the morphological polarization of developing neurons. J Cell Sci 127:4409–4419PubMedCrossRefGoogle Scholar
  56. Gilmore EC, Walsh CA (2013) Genetic causes of microcephaly and lessons for neuronal development. Wiley Interdiscp Rev Dev Biol 2:461–478. doi: 10.1002/wdev.89 CrossRefGoogle Scholar
  57. Gleeson JG (2001) Neuronal migration disorders. Ment Retard Dev Disabil Res Rev 7:167–171PubMedCrossRefGoogle Scholar
  58. Götz M, Huttner WB (2005) The cell biology of neurogenesis. Nat Rev Mol Cell Biol 6:777–788. doi: 10.1038/nrm1739 PubMedCrossRefGoogle Scholar
  59. Gregory W, Edmondson J (1988) Cytology and neuron-glial apposition of migrating cerebellar granule cells in vitro. J Neurosci 8:1728–1738PubMedGoogle Scholar
  60. Haase G, Dessaud E, Garcès A (2002) GDNF acts through PEA3 to regulate cell body positioning and muscle innervation of specific motor neuron pools. Neuron 35:893–905PubMedCrossRefGoogle Scholar
  61. Halbleib JM, Nelson WJ (2006) Cadherins in development: cell adhesion, sorting, and tissue morphogenesis. Genes Dev 20:3199–3214. doi: 10.1101/gad.1486806 PubMedCrossRefGoogle Scholar
  62. Hall BK (2008) The neural crest and neural crest cells in vertebrate development and evolution. TripleC. doi: 10.1007/128 Google Scholar
  63. Hall R, Erickson C (2003) ADAM 10: an active metalloprotease expressed during avian epithelial morphogenesis. Dev Biol 256:146–159PubMedCrossRefGoogle Scholar
  64. Hatakeyama J, Bessho Y, Katoh K et al (2004) Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation. Development 131:5539–5550. doi: 10.1242/dev.01436 PubMedCrossRefGoogle Scholar
  65. Hatakeyama J, Wakamatsu Y, Nagafuchi A et al (2014) Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in vertebrates. Development 141:1671–1682. doi: 10.1242/dev.102988 PubMedCrossRefGoogle Scholar
  66. Hatta K, Takeichi M (1986) Expression of N-cadherin adhesion molecules associated with early morphogenetic events in chick development. Nature 320:447–449. doi: 10.1038/320447a0 PubMedCrossRefGoogle Scholar
  67. Hazan RB, Qiao R, Keren R et al (2004) Cadherin switch in tumor progression. Ann N Y Acad Sci 1014:155–163. doi: 10.1196/annals.1294.016 PubMedCrossRefGoogle Scholar
  68. Higginbotham HR, Gleeson JG (2007) The centrosome in neuronal development. Trends Neurosci 30:276–283PubMedCrossRefGoogle Scholar
  69. Hirano S, Takeichi M (2012) Cadherins in brain morphogenesis and wiring. Physiol Rev 92:597–634PubMedCrossRefGoogle Scholar
  70. Hirano M, Hashimoto S, Yonemura S et al (2008) EPB41L5 functions to post-transcriptionally regulate cadherin and integrin during epithelial-mesenchymal transition. J Cell Biol 182:1217–1230. doi: 10.1083/jcb.200712086 PubMedPubMedCentralCrossRefGoogle Scholar
  71. Hong E, Brewster R (2006) N-cadherin is required for the polarized cell behaviours that drive neurulation in the zebrafish. Development 133:3895–3905. doi: 10.1242/dev.02560 PubMedCrossRefGoogle Scholar
  72. Inuzuka H, Redies C, Takeichi M (1991) Differential expression of R- and N-cadherin in neural and mesodermal tissues during early chicken development. Development 113:959–967PubMedGoogle Scholar
  73. Johnson C, Drgon T, Liu QR et al (2006) Pooled association genome scanning for alcohol dependence using 104,268 SNPs: validation and use to identify alcoholism vulnerability loci in unrelated individuals from the collaborative study on the genetics of alcoholism. Am J Med Genet B Neuropsychiatr Genet 141:844–853CrossRefGoogle Scholar
  74. Junghans D, Hack I, Frotscher M et al (2005) Beta-catenin-mediated cell-adhesion is vital for embryonic forebrain development. Dev Dyn 233:528–539. doi: 10.1002/dvdy.20365 PubMedCrossRefGoogle Scholar
  75. Kadowaki M, Nakamura S, Machon O et al (2007) N-cadherin mediates cortical organization in the mouse brain. Dev Biol 304:22–33PubMedCrossRefGoogle Scholar
  76. Katsamba P, Carroll K, Ahlsen G et al (2009) Linking molecular affinity and cellular specificity in cadherin-mediated adhesion. Proc Natl Acad Sci U S A 106:11594–11599PubMedPubMedCentralCrossRefGoogle Scholar
  77. Kay JN, De la Huerta I, Kim IJ (2011) Retinal ganglion cells with distinct directional preferences differ in molecular identity, structure, and central projections. J Neurosci 31:7753–7762PubMedPubMedCentralCrossRefGoogle Scholar
  78. Kostetskii I, Moore R, Kemler R, Radice GL (2001) Differential adhesion leads to segregation and exclusion of N-cadherin-deficient cells in chimeric embryos. Dev Biol 234:72–79. doi: 10.1006/dbio.2001.0250 PubMedCrossRefGoogle Scholar
  79. Lasky-Su J, Neale BM, Franke B et al (2008) Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. Am J Med Genet B Neuropsychiatr Genet 147:1345–1354CrossRefGoogle Scholar
  80. Lee CH, Gumbiner BM (1995) Disruption of gastrulation movements in Xenopus by a dominant-negative mutant for C-cadherin. Dev Biol 171:363–373. doi: 10.1006/dbio.1995.1288 PubMedCrossRefGoogle Scholar
  81. Lein W-H, Klezovitch O, Fernandez TE, et al (2006) αE-catenin controls cerebral cortical size by regulating hedgehog signalling pathway. 311:1609–1612. doi: 10.1126/science.1121449.
  82. Lepage SE, Bruce AEE (2010) Zebrafish epiboly: mechanics and mechanisms. Int J Dev Biol 54:1213–1228. doi: 10.1387/ijdb.093028sl PubMedCrossRefGoogle Scholar
  83. Lesch KP, Timmesfeld N, Renner TJ et al (2008) Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies. J Neural Transm 115:1573–1585PubMedCrossRefGoogle Scholar
  84. Liu Q, Marrs JA, Azodi E et al (2004) Differential expression of cadherins in the developing and adult zebrafish olfactory system. J Comp Neurol 478:269–281PubMedCrossRefGoogle Scholar
  85. Livet J, Sigrist M, Stroebel S et al (2002) ETS gene Pea3 controls the central position and terminal arborization of specific motor neuron pools. Neuron 35:877–892PubMedCrossRefGoogle Scholar
  86. Lonze BE, Ginty DD (2002) Function and regulation of CREB family transcription factors in the nervous system. Neuron 35:605–623PubMedCrossRefGoogle Scholar
  87. Malinverno M, Carta M, Epis R et al (2010) Synaptic localization and activity of ADAM10 regulate excit- atory synapses through N-cadherin cleavage. J Neurosci 30:16343–16355PubMedCrossRefGoogle Scholar
  88. Marambaud P, Wen PH, Dutt A et al (2003) A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell 114:635–645PubMedCrossRefGoogle Scholar
  89. Marín O, Valiente M, Ge X, Tsai L-H (2010) Guiding neuronal cell migrations. Cold Spring Harb Perspect Biol 2:1–21. doi: 10.1101/cshperspect.a001834 CrossRefGoogle Scholar
  90. Marrs GS, Theisen CS, Bruses JL (2009) N-cadherin modulates voltage activated calcium influx via RhoA, p120-catenin, and myosin-actin interaction. Mol Cell Neurosci 40:390–400PubMedPubMedCentralCrossRefGoogle Scholar
  91. Martin-Belmonte F, Perez-Moreno M (2011) Epithelial cell polarity, stem cells and cancer. Nat Rev Cancer 12:23–38. doi: 10.1038/nrc3169 PubMedGoogle Scholar
  92. Masai I, Lele Z, Yamaguchi M (2003) N-cadherin mediates retinal lamination, maintenance of forebrain compartments and patterning of retinal neurites. Development 130:2479–2494PubMedCrossRefGoogle Scholar
  93. Matsunaga M, Hatta K, Nagafuchi A, Takeichi M (1988a) Guidance of optic nerve fibres by N-cadherin adhesion molecules. Nature 334:62–64PubMedCrossRefGoogle Scholar
  94. Matsunaga M, Hatta K, Takeichi M (1988b) Role of N-cadherin cell adhesion molecules in the histogenesis of neural retina. Neuron 1:289–295. doi: 10.1016/0896-6273(88)90077-3 PubMedCrossRefGoogle Scholar
  95. Matsunaga E, Nambu S, Oka M, Iriki A (2013) Differential cadherin expression in the developing postnatal telencephalon of a New World monkey. J Comp Neurol 521:4027–4060PubMedGoogle Scholar
  96. Mayor R, Theveneau E (2013) The neural crest. Development 140:2247–2251. doi: 10.1242/dev.091751 PubMedCrossRefGoogle Scholar
  97. Medina M, Marinescu RC, Overhauser J, Kosik KS (2000) Hemizygosity of delta-catenin (CTNND2) is associated with severe mental retardation in cri-du-chat syndrome. Genomics 63:157–164PubMedCrossRefGoogle Scholar
  98. Monea S, Jordan BA, Srivastava S et al (2006) Membrane localization of membrane type 5 matrix metalloproteinase by AMPA receptor binding protein and cleavage of cadherins. J Neurosci 26:2300–2312PubMedCrossRefGoogle Scholar
  99. Mysore SP, Tai CY, Schuman EM (2007) Effects of N-cadherin disruption on spine morphological dynamics. Front Cell Neurosci 1:1. doi: 10.3389/neuro.03.001.2007 PubMedPubMedCentralCrossRefGoogle Scholar
  100. Nakagawa S, Takeichi M (1995) Neural crest cell-cell adhesion controlled by sequential and subpopulation-specific expression of novel cadherins. Development 121:1321–1332. doi: 10.1016/0168-9525(95)90550-2 PubMedGoogle Scholar
  101. Nakaya Y, Sheng G (2008) Epithelial to mesenchymal transition during gastrulation: an embryological view. Dev Growth Differ 50:755–766. doi: 10.1111/j.1440-169X.2008.01070.x PubMedCrossRefGoogle Scholar
  102. Nelson J, Nusse R (2004) Convergence of Wnt, β-Catenin, and Cadherin pathways. Science (80–) 303:1483–1487. doi: 10.1126/science.1094291
  103. Nishimura T, Takeichi M (2009) Remodeling of the Adherens Junctions During Morphogenesis. In: Lecuit T (ed) Tissue remodeling and epithelial morphogenesis, 1st edn. Elsevier, San Diego, pp 33–49Google Scholar
  104. Noles SR, Chenn A (2007) Cadherin inhibition of β -catenin signaling regulates the proliferation and differentiation of neural precursor cells. Mol Cell Neurosci 35:549–558. doi: 10.1016/j.mcn.2007.04.012
  105. Nuriya M, Huganir RL (2006) Regulation of AMPA receptor trafficking by N-cadherin. J Neurochem 97:652–661PubMedCrossRefGoogle Scholar
  106. Oblander SA, Brady-Kalnay SM (2010) Distinct PTPmu-associated signaling molecules dif- ferentially regulate neurite outgrowth on E-, N-, and R-cadherin. Mol Cell Neurosci 44:78–93PubMedPubMedCentralCrossRefGoogle Scholar
  107. Oblander SA, Ensslen-Craig SE, Longo FM, Brady-Kalnay SM (2007) E-cadherin promotes retinal ganglion cell neurite outgrowth in a protein tyrosine phosphatase mu dependent manner. Mol Cell Neurosci 34:481–492PubMedPubMedCentralCrossRefGoogle Scholar
  108. Ozair MZ, Kintner C, Brivanlou AH (2013) Neural induction and early patterning in vertebrates. Wiley Interdiscip Rev Dev Biol 2:479–498. doi: 10.1002/wdev.90 PubMedCrossRefGoogle Scholar
  109. Paradis S, Harrar DB, Lin Y et al (2007) An RNAi-based approach identifies molecules required for gluta- matergic and GABAergic synapse development. Neuron 53:217–232PubMedPubMedCentralCrossRefGoogle Scholar
  110. Park K-S, Gumbiner BM (2010) Cadherin 6B induces BMP signaling and de-epithelialization during the epithelial mesenchymal transition of the neural crest. Development 137:2691–2701. doi: 10.1242/dev.050096 PubMedPubMedCentralCrossRefGoogle Scholar
  111. Park K-S, Gumbiner BM (2012) Cadherin-6B stimulates an epithelial mesenchymal transition and the delamination of cells from the neural ectoderm via LIMK/ cofilin mediated non-canonical BMP receptor signaling. Dev Biol 366:232–243. doi: 10.1016/j.biotechadv.2011.08.021.Secreted PubMedPubMedCentralCrossRefGoogle Scholar
  112. Perego C, Vanoni C, Massari S et al (2002) Invasive behaviour of glioblastoma cell lines is associated with altered organisation of the cadherin-catenin adhesion system. J Cell Sci 115:3331–3340PubMedGoogle Scholar
  113. Pollarolo G, Schulz JG, Munck S, Dotti CG (2011) Cytokinesis remnants define first neuronal asymmetry in vivo. Nat Neurosci 14:1525–1533PubMedCrossRefGoogle Scholar
  114. Powell SK, Rivas RJ, Rodriguez-Boulan E, Hatten ME (1997) Development of polarity in cerebellar granule neurons. J Neurobiol 32:223–236PubMedCrossRefGoogle Scholar
  115. Price SR, De Marco GNV, Ranscht B, Jessell TM (2002) Regulation of motor neuron pool sorting by differential expression of type II cadherins. Cell 109:205–16PubMedCrossRefGoogle Scholar
  116. Radice GL, Rayburn H, Matsunami H et al (1997) Developmental defects in mouse embryos lacking N-cadherin. Dev Biol 181:64–78. doi: 10.1006/dbio.1996.8443 PubMedCrossRefGoogle Scholar
  117. Rakic P (2003) Developmental and evolutionary adaptations of cortical radial glia. Cereb Cortex 13:541–549. doi: 10.1093/cercor/13.6.541 PubMedCrossRefGoogle Scholar
  118. Rasin M-R, Gazula V-R, Breunig JJ et al (2007) Numb and Numbl are required for maintenance of cadherin-based adhesion and polarity of neural progenitors. Nat Neurosci 10:819–827. doi: 10.1038/nn1924 PubMedCrossRefGoogle Scholar
  119. Redies C, Takeichi M (1993) N-and R-cadherin expression in the optic nerve of the chicken embryo. Glia 8:161–171PubMedCrossRefGoogle Scholar
  120. Redies C, Engelhart K, Takeichi M (1993) Differential expression of N- and R-cadherin in functional neuronal systems and other structures of the developing chicken brain. J Comp Neurol 333:398–416PubMedCrossRefGoogle Scholar
  121. Reiss K, Maretzky T, Ludwig A et al (2005) ADAM10 cleavage of N-cadherin and regulation of cell-cell adhesion and beta-catenin nuclear signalling. EMBO J 24:742–752PubMedPubMedCentralCrossRefGoogle Scholar
  122. Riehl R, Johnson K, Bradley R et al (1996) Cadherin function is required for axon outgrowth in retinal ganglion cells in vivo. Neuron 17:837–848PubMedCrossRefGoogle Scholar
  123. Rose O, Grund C, Reinhardt S et al (1995) Contactus adherens, a special type of plaque-bearing adhering junction containing M-cadherin, in the granule cell layer of the cerebellar glomerulus. Proc Natl Acad Sci U S A 92:6022–6026PubMedPubMedCentralCrossRefGoogle Scholar
  124. Rousso DL, Pearson CA, Gaber ZB et al (2013) Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS. Neuron 74:314–330. doi: 10.1038/nature11130.Reduced CrossRefGoogle Scholar
  125. Rungger-Brändle E, Ripperger JA, Steiner K et al (2010) Retinal patterning by Pax6-dependent cell adhesion molecules. Dev Neurobiol 70:764–780. doi: 10.1002/dneu.20816 PubMedCrossRefGoogle Scholar
  126. Saglietti L, Dequidt C, Kamieniarz K et al (2007) Extracellular interactions between GluR2 and N-cadherin in spine regulation. Neuron 54:461–477PubMedCrossRefGoogle Scholar
  127. Schiffmacher AT, Padmanabhan R, Jhingory S, Taneyhill LA (2014) Cadherin-6B is proteolytically processed during epithelial-to-mesenchymal transitions of the cranial neural crest. Mol Biol Cell 25:41–54. doi: 10.1091/mbc.E13-08-0459 PubMedPubMedCentralCrossRefGoogle Scholar
  128. Schmid RS, McGrath B, Berechid BE et al (2003) Neuregulin 1-erbB2 signaling is required for the establishment of radial glia and their transformation into astrocytes in cerebral cortex. Proc Natl Acad Sci U S A 100:4251–4256. doi: 10.1073/pnas.0630496100 PubMedPubMedCentralCrossRefGoogle Scholar
  129. Sheng L, Leshchyns’ka I, Sytnyk V (2013) Cell adhesion and intracellular calcium signaling in neurons. Cell Commun Signal 11:94. doi: 10.1186/1478-811X-11-94 PubMedPubMedCentralCrossRefGoogle Scholar
  130. Shikanai M, Nakajima K, Kawauchi T (2011) N-Cadherin regulates radial glial fiber-dependent migration of cortical locomoting neurons. Commun Integr Biol 4:326–330. doi: 10.4161/cib.4.3.14886 PubMedPubMedCentralCrossRefGoogle Scholar
  131. Shimizu T, Yabe T, Muraoka O et al (2005) E-cadherin is required for gastrulation cell movements in zebrafish. Mech Dev 122:747–763. doi: 10.1016/j.mod.2005.03.008 PubMedCrossRefGoogle Scholar
  132. Shimoyama Y, Tsujimoto G, Kitajima M, Natori M (2000) Identification of three human type-II classic cadherins and frequent heterophilic interactions between different subclasses of type-II classic cadherins. Biochem J 349:159–167PubMedPubMedCentralCrossRefGoogle Scholar
  133. Shoval I, Ludwig A, Kalcheim C (2007) Antagonistic roles of full-length N-cadherin and its soluble BMP cleavage product in neural crest delamination. Development 134:491–501. doi: 10.1242/dev.02742 PubMedCrossRefGoogle Scholar
  134. Singh SM, Castellani C, O’Reilly R (2010) Autism meets schizophrenia via cadherin pathway. Schizophr Res 116:293–294PubMedCrossRefGoogle Scholar
  135. Solecki DJ, Model L, Gaetz J (2004) Par6alpha signaling controls glial-guided neuronal migration. Nat Neurosci 7:1195–1203PubMedCrossRefGoogle Scholar
  136. Solnica-Krezel L, Sepich DS (2012) Gastrulation: making and shaping germ layers. Annu Rev Cell Dev Biol 28:687–717PubMedCrossRefGoogle Scholar
  137. Suzuki SC, Takeichi M (2008) Cadherins in neuronal morphogenesis and function. Dev Growth Differ 1:S119–S130CrossRefGoogle Scholar
  138. Swartling FJ, Savov V, Persson AI et al (2012) Distinct neural stem cell populations give rise to disparate brain tumors in response to N-MYC. Cancer Cell 21:601–613. doi: 10.1016/j.ccr.2012.04.012 PubMedPubMedCentralCrossRefGoogle Scholar
  139. Tai CY, Mysore SP, Chiu C, Schuman EM (2007) Activity-regulated N-cadherin endocytosis. Neuron 54:771–785PubMedCrossRefGoogle Scholar
  140. Tai CY, Kim SA, Schuman EM (2008) Cadherins and synaptic plasticity. Curr Opin Cell Biol 20:567–575PubMedCrossRefGoogle Scholar
  141. Takahashi T, Nowakowski RS, Caviness VS (1993) Cell cycle parameters and patterns of nuclear movement in the neocortical proliferative zone of the fetal mouse. J Neurosci 13:820–833PubMedGoogle Scholar
  142. Takeichi M (2007) The cadherin superfamily in neuronal connections and interactions. Nat Rev Neurosci 8:11–20PubMedCrossRefGoogle Scholar
  143. Takeichi M, Inuzuka H, Shimamura K et al (1990) Cadherin subclasses: differential expression and their roles in neural morphogenesis. Cold Spring Harb Symp Quant Biol 55:319–325PubMedCrossRefGoogle Scholar
  144. Tanabe K, Takahashi Y, Sato Y et al (2006) Cadherin is required for dendritic morphogenesis and synaptic terminal organization of retinal horizontal cells. Development 133:4085–4096PubMedCrossRefGoogle Scholar
  145. Tanaka T, Serneo FF, Higgins C et al (2004) Lis1 and doublecortin function with dynein to mediate coupling of the nucleus to the centrosome in neuronal migration. J Cell Biol 165:709–721PubMedPubMedCentralCrossRefGoogle Scholar
  146. Taneyhill LA, Schiffmacher AT (2013) Chapter 3: The Cell Biology of Neural Crest Cell Delamination and EMT. In: Trainor P (ed) Neural Crest Cells: Evolution, Development and Disease. Elsevier Inc, Taramani, pp 1–22Google Scholar
  147. Taneyhill LA, Coles EG, Bronner-Fraser M (2007) Snail2 directly represses cadherin6B during epithelial-to-mesenchymal transitions of the neural crest. Development 134:1481–1490. doi: 10.1242/dev.02834 PubMedPubMedCentralCrossRefGoogle Scholar
  148. Temple S (2001) The development of neural stem cells. Nature 414:112–117. doi: 10.1038/35102174 PubMedCrossRefGoogle Scholar
  149. Teng J, Rai T, Tanaka Y et al (2005) The KIF3 motor transports N-cadherin and organizes the developing neuroepithelium. Nat Cell Biol 7:474–482. doi: 10.1038/ncb1249 PubMedCrossRefGoogle Scholar
  150. Tepass U, Truong K, Godt D et al (2000) Cadherins in embryonic and neural morphogenesis. Nat Rev Mol Cell Biol 1:91–100. doi: 10.1038/35040042 PubMedCrossRefGoogle Scholar
  151. Thalhammer A, Cingolani LA (2014) Cell adhesion and homeostatic synaptic plasticity. Neuropharmacology 78:23–30PubMedCrossRefGoogle Scholar
  152. Theveneau E, Mayor R (2012) Neural crest delamination and migration: from epithelium-to-mesenchyme transition to collective cell migration. Dev Biol 366:34–54. doi: 10.1016/j.ydbio.2011.12.041 PubMedCrossRefGoogle Scholar
  153. Thiery JP, Acloque H, Huang RYJ, Nieto MA (2009) Epithelial-Mesenchymal Transitions in Development and Disease. Cell 139:871–890. doi: 10.1016/j.cell.2009.11.007 PubMedCrossRefGoogle Scholar
  154. Togashi H, Abe K, Mizoguchi A et al (2002) Cadherin regulates dendritic spine morphogenesis. Neuron 35:77–89PubMedCrossRefGoogle Scholar
  155. Tomaselli KJ, Neugebauer KM, Bixby JL et al (1988) N-cadherin and integrins: two receptor systems that mediate neuronal process outgrowth on astrocyte surfaces. Neuron 1:33–43PubMedCrossRefGoogle Scholar
  156. Treutlein J, Cichon S, Ridinger M et al (2009) Genome-wide association study of alcohol dependence. Arch Gen Psychiatry 66:773–784PubMedPubMedCentralCrossRefGoogle Scholar
  157. Tsuchiya B, Sato Y, Kameya T et al (2006) Differential expression of N-cadherin and E-cadherin in normal human tissues. Arch Histol Cytol 69:135–145PubMedCrossRefGoogle Scholar
  158. Uchida N, Honjo Y, Johnson KR et al (1996) The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones. J Cell Biol 135:767–779PubMedCrossRefGoogle Scholar
  159. Uemura K, Kihara T, Kuzuya A et al (2006) Characterization of sequential N-cadherin cleavage by ADAM10 and PS1. Neurosci Lett 402:278–283PubMedCrossRefGoogle Scholar
  160. Vallin J, Girault JM, Thiery JP, Broders F (1998) Xenopus cadherin-11 is expressed in different populations of migrating neural crest cells. Mech Dev 75:171–174. doi: 10.1016/S0925-4773(98)00099-9 PubMedCrossRefGoogle Scholar
  161. Wang K, Zhang H, Ma D et al (2009) Common genetic variants on 5p14.1 associate with autism spectrum dis- orders. Nature 459:528–533PubMedPubMedCentralCrossRefGoogle Scholar
  162. Zhadanov AB, Provance DW, Speer CA et al (1999) Absence of the tight junctional protein AF-6 disrupts epithelial cell-cell junctions and cell polarity during mouse development. Curr Biol 9:880–888. doi: 10.1016/S0960-9822(99)80392-3 PubMedCrossRefGoogle Scholar
  163. Zhang J, Woodhead GJ, Swaminathan SK et al (2010) Cortical neural precursors inhibit their own differentiation via N- cadherin maintenance of beta-catenin signaling. Dev Cell 18:472–479. doi: 10.1016/j.devcel.2009.12.025.Cortical PubMedPubMedCentralCrossRefGoogle Scholar
  164. Zhang J, Shemezis JR, Mcquinn ER et al (2013) AKT activation by N-cadherin regulates beta-catenin signaling and neuronal differentiation during cortical development. Neural Dev 8:1. doi: 10.1186/1749-8104-8-7 CrossRefGoogle Scholar
  165. Zhong Y, Brieher WM, Gumbiner BM (1999) Analysis of C-cadherin regulation during tissue morphogenesis with an activating antibody. J Cell Biol 144:351–359. doi: 10.1083/jcb.144.2.351 PubMedPubMedCentralCrossRefGoogle Scholar
  166. Zhu X, Zhang J, Tollkuhn J et al (2006) Sustained Notch signaling in progenitors is required for sequential emergence of distinct cell lineages during organogenesis. Genes Dev 20:2739–2753. doi: 10.1101/gad.1444706 PubMedPubMedCentralCrossRefGoogle Scholar
  167. Zmuda JF, Rivas RJ (1998) The Golgi apparatus and the centrosome are localized to the sites of newly emerging axons in cerebellar granule neurons in vitro. Cell Motil Cytoskel 41:18–38CrossRefGoogle Scholar
  168. Zohn IE, Li Y, Skolnik EY et al (2006) p38 and a p38-Interacting Protein Are Critical for Downregulation of E-Cadherin during Mouse Gastrulation. Cell 125:957–969. doi: 10.1016/j.cell.2006.03.048 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2016

Authors and Affiliations

  1. 1.Research Department of Cell and Developmental BiologyUniversity College LondonLondonUK

Personalised recommendations