Spatiotemporal coordination of cellular differentiation and tissue morphogenesis in organ of Corti development



The organ of Corti, an acoustic sensory organ, is a specifically differentiated epithelium of the cochlear duct, which is a part of the membranous labyrinth in the inner ear. Cells in the organ of Corti are generally classified into two kinds; hair cells, which transduce the mechanical stimuli of sound to the cell membrane electrical potential differences, and supporting cells. These cells emerge from homogeneous prosensory epithelium through cell fate determination and differentiation. In the organ of Corti organogenesis, cell differentiation and the rearrangement of their position proceed in parallel, resulting in a characteristic alignment of mature hair cells and supporting cells. Recently, studies have focused on the signaling molecules and transcription factors that regulate cell fate determination and differentiation processes. In comparison, less is known about the mechanism of the formation of the tissue architecture; however, this is important in the morphogenesis of the organ of Corti. Thus, this review will introduce previous findings that focus on how cell fate determination, cell differentiation, and whole tissue morphogenesis proceed in a spatiotemporally and finely coordinated manner. This overview provides an insight into the regulatory mechanisms of the coordination in the developing organ of Corti.


Organ of Corti Hair cells Development Cell fate determination Cellular differentiation Convergent extension Morphogenesis 


Compliance with ethical standards

Conflict of interest

The author has no conflicts of interest to declare.


  1. 1.
    Atkinson PJ, Huarcaya Najarro E, Sayyid ZN, Cheng AG (2015) Sensory hair cell development and regeneration: similarities and differences. Development 142:1561–1571. PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Basch ML, Brown RM II, Jen HI, Groves AK (2016) Where hearing starts: the development of the mammalian cochlea. J Anat 228:233–254. PubMedCrossRefGoogle Scholar
  3. 3.
    Huh SH, Jones J, Warchol ME, Ornitz DM (2012) Differentiation of the lateral compartment of the cochlea requires a temporally restricted FGF20 signal. PLoS Biol 10:e1001231. PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Gillespie PG, Muller U (2009) Mechanotransduction by hair cells: models, molecules, and mechanisms. Cell 139:33–44. PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Bulankina AV, Moser T (2012) Neural circuit development in the mammalian cochlea. Physiology (Bethesda) 27:100–112. Google Scholar
  6. 6.
    Kelley MW (2006) Regulation of cell fate in the sensory epithelia of the inner ear. Nat Rev Neurosci 7:837–849. PubMedCrossRefGoogle Scholar
  7. 7.
    Kelley MW (2002) Determination and commitment of mechanosensory hair cells. Sci World J 2:1079–1094. CrossRefGoogle Scholar
  8. 8.
    Parsa A, Webster P, Kalinec F (2012) Deiters cells tread a narrow path–the Deiters cells-basilar membrane junction. Hear Res 290:13–20. PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Soons JA, Ricci AJ, Steele CR, Puria S (2015) Cytoarchitecture of the mouse organ of corti from base to apex, determined using in situ two-photon imaging. J Assoc Res Otolaryngol 16:47–66. PubMedCrossRefGoogle Scholar
  10. 10.
    Karavitaki KD, Mountain DC (2007) Imaging electrically evoked micromechanical motion within the organ of corti of the excised gerbil cochlea. Biophys J 92:3294–3316. PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Bryant J, Goodyear RJ, Richardson GP (2002) Sensory organ development in the inner ear: molecular and cellular mechanisms. Br Med Bull 63:39–57PubMedCrossRefGoogle Scholar
  12. 12.
    Ohyama T, Mohamed OA, Taketo MM, Dufort D, Groves AK (2006) Wnt signals mediate a fate decision between otic placode and epidermis. Development 133:865–875. PubMedCrossRefGoogle Scholar
  13. 13.
    Riccomagno MM, Takada S, Epstein DJ (2005) Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh. Genes Dev 19:1612–1623. PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Wu DK, Kelley MW (2012) Molecular mechanisms of inner ear development. Cold Spring Harb Perspect Biol 4:a008409. PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Kiernan AE, Pelling AL, Leung KK, Tang AS, Bell DM, Tease C, Lovell-Badge R, Steel KP, Cheah KS (2005) Sox2 is required for sensory organ development in the mammalian inner ear. Nature 434:1031–1035. PubMedCrossRefGoogle Scholar
  16. 16.
    Kiernan AE, Xu J, Gridley T (2006) The Notch ligand JAG1 is required for sensory progenitor development in the mammalian inner ear. PLoS Genet 2:e4. PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Basch ML, Ohyama T, Segil N, Groves AK (2011) Canonical Notch signaling is not necessary for prosensory induction in the mouse cochlea: insights from a conditional mutant of RBPjkappa. J Neurosci 31:8046–8058. PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Munnamalai V, Hayashi T, Bermingham-McDonogh O (2012) Notch prosensory effects in the Mammalian cochlea are partially mediated by Fgf20. J Neurosci 32:12876–12884. PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Ono K, Kita T, Sato S, O’Neill P, Mak SS, Paschaki M, Ito M, Gotoh N, Kawakami K, Sasai Y, Ladher RK (2014) FGFR1-Frs2/3 signalling maintains sensory progenitors during inner ear hair cell formation. PLoS Genet 10:e1004118. PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Ohyama T, Basch ML, Mishina Y, Lyons KM, Segil N, Groves AK (2010) BMP signaling is necessary for patterning the sensory and nonsensory regions of the developing mammalian cochlea. J Neurosci 30:15044–15051. PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Kelley MW (2007) Cellular commitment and differentiation in the organ of Corti. Int J Dev Biol 51:571–583. PubMedCrossRefGoogle Scholar
  22. 22.
    Qian D, Jones C, Rzadzinska A, Mark S, Zhang X, Steel KP, Dai X, Chen P (2007) Wnt5a functions in planar cell polarity regulation in mice. Dev Biol 306:121–133. PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Bohnenpoll T, Trowe MO, Wojahn I, Taketo MM, Petry M, Kispert A (2014) Canonical Wnt signaling regulates the proliferative expansion and differentiation of fibrocytes in the murine inner ear. Dev Biol 391:54–65. PubMedCrossRefGoogle Scholar
  24. 24.
    Chai R, Xia A, Wang T, Jan TA, Hayashi T, Bermingham-McDonogh O, Cheng AG (2011) Dynamic expression of Lgr5, a Wnt target gene, in the developing and mature mouse cochlea. J Assoc Res Otolaryngol 12:455–469. PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Munnamalai V, Fekete DM (2016) Notch-Wnt-Bmp crosstalk regulates radial patterning in the mouse cochlea in a spatiotemporal manner. Development 143:4003–4015. PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Takahashi K, Kamiya K, Urase K, Suga M, Takizawa T, Mori H, Yoshikawa Y, Ichimura K, Kuida K, Momoi T (2001) Caspase-3-deficiency induces hyperplasia of supporting cells and degeneration of sensory cells resulting in the hearing loss. Brain Res 894:359–367PubMedCrossRefGoogle Scholar
  27. 27.
    Kamiya K, Takahashi K, Kitamura K, Momoi T, Yoshikawa Y (2001) Mitosis and apoptosis in postnatal auditory system of the C3H/He strain. Brain Res 901:296–302PubMedCrossRefGoogle Scholar
  28. 28.
    Fekete DM (2009) Cochlear development. Encycl Neurosci. Google Scholar
  29. 29.
    Ruben RJ (1967) Development of the inner ear of the mouse: a radioautographic study of terminal mitoses. Acta Otolaryngol 220:1–44Google Scholar
  30. 30.
    Heywood P, Van de Water TR, Hilding DA, Ruben RJ (1975) Distribution of microtubules and microfilaments in developing vestibular sensory epithelium of mouse otocysts grown in vitro. J Cell Sci 17:171–189PubMedGoogle Scholar
  31. 31.
    Chen P, Segil N (1999) p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti. Development 126:1581–1590PubMedGoogle Scholar
  32. 32.
    Lee YS, Liu F, Segil N (2006) A morphogenetic wave of p27Kip1 transcription directs cell cycle exit during organ of Corti development. Development 133:2817–2826. PubMedCrossRefGoogle Scholar
  33. 33.
    Matei V, Pauley S, Kaing S, Rowitch D, Beisel KW, Morris K, Feng F, Jones K, Lee J, Fritzsch B (2005) Smaller inner ear sensory epithelia in Neurog 1 null mice are related to earlier hair cell cycle exit. Dev Dyn 234:633–650. PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Jahan I, Pan N, Kersigo J, Fritzsch B (2010) Neurod1 suppresses hair cell differentiation in ear ganglia and regulates hair cell subtype development in the cochlea. PLoS One 5:e11661. PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Ma Q, Chen Z, del Barco Barrantes I, de la Pompa JL, Anderson DJ (1998) neurogenin1 is essential for the determination of neuronal precursors for proximal cranial sensory ganglia. Neuron 20:469–482PubMedCrossRefGoogle Scholar
  36. 36.
    Liu M, Pereira FA, Price SD, Chu MJ, Shope C, Himes D, Eatock RA, Brownell WE, Lysakowski A, Tsai MJ (2000) Essential role of BETA2/NeuroD1 in development of the vestibular and auditory systems. Genes Dev 14:2839–2854PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Kruger M, Schmid T, Kruger S, Bober E, Braun T (2006) Functional redundancy of NSCL-1 and NeuroD during development of the petrosal and vestibulocochlear ganglia. Eur J Neurosci 24:1581–1590. PubMedCrossRefGoogle Scholar
  38. 38.
    Liu Z, Owen T, Zhang L, Zuo J (2010) Dynamic expression pattern of Sonic hedgehog in developing cochlear spiral ganglion neurons. Dev Dyn 239:1674–1683. PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Bok J, Zenczak C, Hwang CH, Wu DK (2013) Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells. Proc Natl Acad Sci USA 110:13869–13874. PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Tateya T, Imayoshi I, Tateya I, Hamaguchi K, Torii H, Ito J, Kageyama R (2013) Hedgehog signaling regulates prosensory cell properties during the basal-to-apical wave of hair cell differentiation in the mammalian cochlea. Development 140:3848–3857. PubMedCrossRefGoogle Scholar
  41. 41.
    Doe CQ (2008) Neural stem cells: balancing self-renewal with differentiation. Development 135:1575–1587. PubMedCrossRefGoogle Scholar
  42. 42.
    Eddison M, Le Roux I, Lewis J (2000) Notch signaling in the development of the inner ear: lessons from Drosophila. Proc Natl Acad Sci USA 97:11692–11699. PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Eddison M, Weber SJ, Ariza-McNaughton L, Lewis J, Daudet N (2015) Numb is not a critical regulator of Notch-mediated cell fate decisions in the developing chick inner ear. Front Cell Neurosci 9:74. PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Fekete DM, Muthukumar S, Karagogeos D (1998) Hair cells and supporting cells share a common progenitor in the avian inner ear. J Neurosci 18:7811–7821PubMedGoogle Scholar
  45. 45.
    Bermingham NA, Hassan BA, Price SD, Vollrath MA, Ben-Arie N, Eatock RA, Bellen HJ, Lysakowski A, Zoghbi HY (1999) Math1: an essential gene for the generation of inner ear hair cells. Science 284:1837–1841PubMedCrossRefGoogle Scholar
  46. 46.
    Jahan I, Pan N, Elliott KL, Fritzsch B (2015) The quest for restoring hearing: understanding ear development more completely. Bioessays 37:1016–1027. PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Shi F, Cheng YF, Wang XL, Edge AS (2010) Beta-catenin up-regulates Atoh1 expression in neural progenitor cells by interaction with an Atoh1 3′ enhancer. J Biol Chem 285:392–400. PubMedCrossRefGoogle Scholar
  48. 48.
    Shi F, Hu L, Jacques BE, Mulvaney JF, Dabdoub A, Edge AS (2014) beta-Catenin is required for hair-cell differentiation in the cochlea. J Neurosci 34:6470–6479. PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Adam J, Myat A, Le Roux I, Eddison M, Henrique D, Ish-Horowicz D, Lewis J (1998) Cell fate choices and the expression of Notch, Delta and Serrate homologues in the chick inner ear: parallels with Drosophila sense-organ development. Development 125:4645–4654PubMedGoogle Scholar
  50. 50.
    Lanford PJ, Lan Y, Jiang R, Lindsell C, Weinmaster G, Gridley T, Kelley MW (1999) Notch signalling pathway mediates hair cell development in mammalian cochlea. Nat Genet 21:289–292. PubMedCrossRefGoogle Scholar
  51. 51.
    Sprinzak D, Lakhanpal A, Lebon L, Santat LA, Fontes ME, Anderson GA, Garcia-Ojalvo J, Elowitz MB (2010) Cis-interactions between Notch and Delta generate mutually exclusive signalling states. Nature 465:86–90. PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Kiernan AE, Cordes R, Kopan R, Gossler A, Gridley T (2005) The Notch ligands DLL1 and JAG2 act synergistically to regulate hair cell development in the mammalian inner ear. Development 132:4353–4362. PubMedCrossRefGoogle Scholar
  53. 53.
    Barad O, Hornstein E, Barkai N (2011) Robust selection of sensory organ precursors by the Notch-Delta pathway. Curr Opin Cell Biol 23:663–667. PubMedCrossRefGoogle Scholar
  54. 54.
    Abdolazimi Y, Stojanova Z, Segil N (2016) Selection of cell fate in the organ of Corti involves the integration of Hes/Hey signaling at the Atoh1 promoter. Development 143:841–850. PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Neves J, Abello G, Petrovic J, Giraldez F (2013) Patterning and cell fate in the inner ear: a case for Notch in the chicken embryo. Dev Growth Differ 55:96–112. PubMedCrossRefGoogle Scholar
  56. 56.
    Petrovic J, Formosa-Jordan P, Luna-Escalante JC, Abello G, Ibanes M, Neves J, Giraldez F (2014) Ligand-dependent Notch signaling strength orchestrates lateral induction and lateral inhibition in the developing inner ear. Development 141:2313–2324. PubMedCrossRefGoogle Scholar
  57. 57.
    Basch ML, Brown RM, Jen HI, Semerci F, Depreux F, Edlund RK, Zhang H, Norton CR, Gridley T, Cole SE, Doetzlhofer A, Maletic-Savatic M, Segil N, Groves AK (2016) Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates. Elife 5. Google Scholar
  58. 58.
    Bermingham-McDonogh O, Oesterle EC, Stone JS, Hume CR, Huynh HM, Hayashi T (2006) Expression of Prox1 during mouse cochlear development. J Comp Neurol 496:172–186. PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Dabdoub A, Puligilla C, Jones JM, Fritzsch B, Cheah KS, Pevny LH, Kelley MW (2008) Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea. Proc Natl Acad Sci USA 105:18396–18401. PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    McKenzie E, Krupin A, Kelley MW (2004) Cellular growth and rearrangement during the development of the mammalian organ of Corti. Dev Dyn 229:802–812. PubMedCrossRefGoogle Scholar
  61. 61.
    Irvine KD (1999) Fringe, Notch, and making developmental boundaries. Curr Opin Genet Dev 9:434–441. PubMedCrossRefGoogle Scholar
  62. 62.
    Bruckner K, Perez L, Clausen H, Cohen S (2000) Glycosyltransferase activity of fringe modulates notch-delta interactions. Nature 406:411–415. PubMedCrossRefGoogle Scholar
  63. 63.
    Hayashi T, Cunningham D, Bermingham-McDonogh O (2007) Loss of Fgfr3 leads to excess hair cell development in the mouse organ of Corti. Dev Dyn 236:525–533. PubMedCrossRefGoogle Scholar
  64. 64.
    Jacques BE, Montcouquiol ME, Layman EM, Lewandoski M, Kelley MW (2007) Fgf8 induces pillar cell fate and regulates cellular patterning in the mammalian cochlea. Development 134:3021–3029. PubMedCrossRefGoogle Scholar
  65. 65.
    Doetzlhofer A, Basch ML, Ohyama T, Gessler M, Groves AK, Segil N (2009) Hey2 regulation by FGF provides a Notch-independent mechanism for maintaining pillar cell fate in the organ of Corti. Dev Cell 16:58–69. PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Puligilla C, Feng F, Ishikawa K, Bertuzzi S, Dabdoub A, Griffith AJ, Fritzsch B, Kelley MW (2007) Disruption of fibroblast growth factor receptor 3 signaling results in defects in cellular differentiation, neuronal patterning, and hearing impairment. Dev Dyn 236:1905–1917. PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Hayashi T, Ray CA, Bermingham-McDonogh O (2008) Fgf20 is required for sensory epithelial specification in the developing cochlea. J Neurosci 28:5991–5999. PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Hayashi T, Ray CA, Younkins C, Bermingham-McDonogh O (2010) Expression patterns of FGF receptors in the developing mammalian cochlea. Dev Dyn 239:1019–1026. PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Pirvola U, Ylikoski J, Trokovic R, Hebert JM, McConnell SK, Partanen J (2002) FGFR1 is required for the development of the auditory sensory epithelium. Neuron 35:671–680PubMedCrossRefGoogle Scholar
  70. 70.
    Holley M, Rhodes C, Kneebone A, Herde MK, Fleming M, Steel KP (2010) Emx2 and early hair cell development in the mouse inner ear. Dev Biol 340:547–556. PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Brooker R, Hozumi K, Lewis J (2006) Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear. Development 133:1277–1286. PubMedCrossRefGoogle Scholar
  72. 72.
    Chen P, Johnson JE, Zoghbi HY, Segil N (2002) The role of Math1 in inner ear development: uncoupling the establishment of the sensory primordium from hair cell fate determination. Development 129:2495–2505PubMedCrossRefGoogle Scholar
  73. 73.
    Cai T, Seymour ML, Zhang H, Pereira FA, Groves AK (2013) Conditional deletion of Atoh1 reveals distinct critical periods for survival and function of hair cells in the organ of Corti. J Neurosci 33:10110–10122. PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Heidrych P, Zimmermann U, Kuhn S, Franz C, Engel J, Duncker SV, Hirt B, Pusch CM, Ruth P, Pfister M, Marcotti W, Blin N, Knipper M (2009) Otoferlin interacts with myosin VI: implications for maintenance of the basolateral synaptic structure of the inner hair cell. Hum Mol Genet 18:2779–2790. PubMedCrossRefGoogle Scholar
  75. 75.
    Roux I, Hosie S, Johnson SL, Bahloul A, Cayet N, Nouaille S, Kros CJ, Petit C, Safieddine S (2009) Myosin VI is required for the proper maturation and function of inner hair cell ribbon synapses. Hum Mol Genet 18:4615–4628. PubMedCrossRefGoogle Scholar
  76. 76.
    Kappler JA, Starr CJ, Chan DK, Kollmar R, Hudspeth AJ (2004) A nonsense mutation in the gene encoding a zebrafish myosin VI isoform causes defects in hair-cell mechanotransduction. Proc Natl Acad Sci USA 101:13056–13061. PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Hertzano R, Shalit E, Rzadzinska AK, Dror AA, Song L, Ron U, Tan JT, Shitrit AS, Fuchs H, Hasson T, Ben-Tal N, Sweeney HL, de Angelis MH, Steel KP, Avraham KB (2008) A Myo6 mutation destroys coordination between the myosin heads, revealing new functions of myosin VI in the stereocilia of mammalian inner ear hair cells. PLoS Genet 4:e1000207. PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Xiang M, Gao WQ, Hasson T, Shin JJ (1998) Requirement for Brn-3c in maturation and survival, but not in fate determination of inner ear hair cells. Development 125:3935–3946PubMedGoogle Scholar
  79. 79.
    Ezan J, Lasvaux L, Gezer A, Novakovic A, May-Simera H, Belotti E, Lhoumeau AC, Birnbaumer L, Beer-Hammer S, Borg JP, Le Bivic A, Nurnberg B, Sans N, Montcouquiol M (2013) Primary cilium migration depends on G-protein signalling control of subapical cytoskeleton. Nat Cell Biol 15:1107–1115. PubMedCrossRefGoogle Scholar
  80. 80.
    Driver EC, Sillers L, Coate TM, Rose MF, Kelley MW (2013) The Atoh1-lineage gives rise to hair cells and supporting cells within the mammalian cochlea. Dev Biol 376:86–98. PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Cotanche DA, Kaiser CL (2010) Hair cell fate decisions in cochlear development and regeneration. Hear Res 266:18–25. PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Wang J, Mark S, Zhang X, Qian D, Yoo SJ, Radde-Gallwitz K, Zhang Y, Lin X, Collazo A, Wynshaw-Boris A, Chen P (2005) Regulation of polarized extension and planar cell polarity in the cochlea by the vertebrate PCP pathway. Nat Genet 37:980–985. PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Montcouquiol M, Rachel RA, Lanford PJ, Copeland NG, Jenkins NA, Kelley MW (2003) Identification of Vangl2 and Scrb1 as planar polarity genes in mammals. Nature 423:173–177. PubMedCrossRefGoogle Scholar
  84. 84.
    Chacon-Heszele MF, Ren D, Reynolds AB, Chi F, Chen P (2012) Regulation of cochlear convergent extension by the vertebrate planar cell polarity pathway is dependent on p120-catenin. Development 139:968–978. PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Iizuka-Kogo A, Senda T, Akiyama T, Shimomura A, Nomura R, Hasegawa Y, Yamamura K, Kogo H, Sawai N, Matsuzaki T (2015) Requirement of DLG1 for cardiovascular development and tissue elongation during cochlear, enteric, and skeletal development: possible role in convergent extension. PLoS One 10:e0123965. PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Simons M, Mlodzik M (2008) Planar cell polarity signaling: from fly development to human disease. Annu Rev Genet 42:517–540. PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Tada M, Heisenberg CP (2012) Convergent extension: using collective cell migration and cell intercalation to shape embryos. Development 139:3897–3904. PubMedCrossRefGoogle Scholar
  88. 88.
    Irvine KD, Wieschaus E (1994) Cell intercalation during Drosophila germband extension and its regulation by pair-rule segmentation genes. Development 120:827–841PubMedGoogle Scholar
  89. 89.
    Bertet C, Sulak L, Lecuit T (2004) Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation. Nature 429:667–671. PubMedCrossRefGoogle Scholar
  90. 90.
    Blankenship JT, Backovic ST, Sanny JS, Weitz O, Zallen JA (2006) Multicellular rosette formation links planar cell polarity to tissue morphogenesis. Dev Cell 11:459–470. PubMedCrossRefGoogle Scholar
  91. 91.
    Dabdoub A, Donohue MJ, Brennan A, Wolf V, Montcouquiol M, Sassoon DA, Hseih JC, Rubin JS, Salinas PC, Kelley MW (2003) Wnt signaling mediates reorientation of outer hair cell stereociliary bundles in the mammalian cochlea. Development 130:2375–2384PubMedCrossRefGoogle Scholar
  92. 92.
    Lu X, Borchers AG, Jolicoeur C, Rayburn H, Baker JC, Tessier-Lavigne M (2004) PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. Nature 430:93–98. PubMedCrossRefGoogle Scholar
  93. 93.
    Montcouquiol M, Sans N, Huss D, Kach J, Dickman JD, Forge A, Rachel RA, Copeland NG, Jenkins NA, Bogani D, Murdoch J, Warchol ME, Wenthold RJ, Kelley MW (2006) Asymmetric localization of Vangl2 and Fz3 indicate novel mechanisms for planar cell polarity in mammals. J Neurosci 26:5265–5275. PubMedCrossRefGoogle Scholar
  94. 94.
    Yamamoto N, Okano T, Ma X, Adelstein RS, Kelley MW (2009) Myosin II regulates extension, growth and patterning in the mammalian cochlear duct. Development 136:1977–1986. PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Lee J, Andreeva A, Sipe CW, Liu L, Cheng A, Lu X (2012) PTK7 regulates myosin II activity to orient planar polarity in the mammalian auditory epithelium. Curr Biol 22:956–966. PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Lye CM, Blanchard GB, Naylor HW, Muresan L, Huisken J, Adams RJ, Sanson B (2015) Mechanical coupling between endoderm invagination and axis extension in drosophila. PLoS Biol 13:e1002292. PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Kong D, Wolf F, Grosshans J (2017) Forces directing germ-band extension in Drosophila embryos. Mech Dev 144:11–22. PubMedCrossRefGoogle Scholar
  98. 98.
    Collinet C, Rauzi M, Lenne PF, Lecuit T (2015) Local and tissue-scale forces drive oriented junction growth during tissue extension. Nat Cell Biol 17:1247–1258. PubMedCrossRefGoogle Scholar
  99. 99.
    Togashi H (2016) Differential and cooperative cell adhesion regulates cellular pattern in sensory epithelia. Front Cell Dev Biol 4:104. PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Samanta D, Almo SC (2015) Nectin family of cell-adhesion molecules: structural and molecular aspects of function and specificity. Cell Mol Life Sci 72:645–658. PubMedCrossRefGoogle Scholar
  101. 101.
    Togashi H, Kominami K, Waseda M, Komura H, Miyoshi J, Takeichi M, Takai Y (2011) Nectins establish a checkerboard-like cellular pattern in the auditory epithelium. Science 333:1144–1147. PubMedCrossRefGoogle Scholar
  102. 102.
    Fukuda T, Kominami K, Wang S, Togashi H, Hirata K, Mizoguchi A, Rikitake Y, Takai Y (2014) Aberrant cochlear hair cell attachments caused by Nectin-3 deficiency result in hair bundle abnormalities. Development 141:399–409. PubMedCrossRefGoogle Scholar
  103. 103.
    Rodgers RJ, Lavranos TC, van Wezel IL, Irving-Rodgers HF (1999) Development of the ovarian follicular epithelium. Mol Cell Endocrinol 151:171–179PubMedCrossRefGoogle Scholar
  104. 104.
    Zhang Y, Yeh LK, Zhang S, Call M, Yuan Y, Yasunaga M, Kao WW, Liu CY (2015) Wnt/beta-catenin signaling modulates corneal epithelium stratification via inhibition of Bmp4 during mouse development. Development 142:3383–3393. PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Que J (2015) The initial establishment and epithelial morphogenesis of the esophagus: a new model of tracheal-esophageal separation and transition of simple columnar into stratified squamous epithelium in the developing esophagus. Wiley Interdiscip Rev Dev Biol 4:419–430. PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Rishniw M, Rodriguez P, Que J, Burke ZD, Tosh D, Chen H, Chen X (2011) Molecular aspects of esophageal development. Ann N Y Acad Sci 1232:309–315. PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Carroll DK, Carroll JS, Leong CO, Cheng F, Brown M, Mills AA, Brugge JS, Ellisen LW (2006) p63 regulates an adhesion programme and cell survival in epithelial cells. Nat Cell Biol 8:551–561. PubMedCrossRefGoogle Scholar
  108. 108.
    Terrinoni A, Serra V, Bruno E, Strasser A, Valente E, Flores ER, van Bokhoven H, Lu X, Knight RA, Melino G (2013) Role of p63 and the Notch pathway in cochlea development and sensorineural deafness. Proc Natl Acad Sci USA 110:7300–7305. PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© The Japanese Society for Clinical Molecular Morphology 2018

Authors and Affiliations

  1. 1.Department of Anatomy and Cell BiologyGunma University Graduate School of MedicineMaebashi CityJapan

Personalised recommendations