{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:31:57Z","timestamp":1790371917467,"version":"4.1.0"},"reference-count":55,"publisher":"The Company of Biologists","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,4,15]]},"abstract":"<jats:p>In developing vertebrates, the neural tube forms from a sheet of neural ectoderm by complex cell movements and morphogenesis. Convergent extension movements and the apical constriction along with apical-basal elongation of cells in the neural ectoderm are thought to be essential for the neural tube closure (NTC) process. In addition, it is known that non-neural ectoderm also plays a crucial role in this process, as the neural tube fails to close in the absence of this tissue in chick and axolotl. However, the cellular and molecular mechanisms by which it functions in NTC are as yet unclear. We demonstrate here that the non-neural superficial epithelium moves in the direction of tensile forces applied along the dorsal-ventral axis during NTC. We found that this force is partly attributable to the deep layer of non-neural ectoderm cells, which moved collectively towards the dorsal midline along with the superficial layer. Moreover, inhibition of this movement by deleting integrin \u03b21 function resulted in incomplete NTC. Furthermore, we demonstrated that other proposed mechanisms, such as oriented cell division, cell rearrangement and cell-shape changes have no or only minor roles in the non-neural movement. This study is the first to demonstrate dorsally oriented deep-cell migration in non-neural ectoderm, and suggests that a global reorganization of embryo tissues is involved in NTC.<\/jats:p>","DOI":"10.1242\/dev.073239","type":"journal-article","created":{"date-parts":[[2012,3,3]],"date-time":"2012-03-03T04:09:59Z","timestamp":1330747799000},"page":"1417-1426","source":"Crossref","is-referenced-by-count":49,"title":["Cell movements of the deep layer of non-neural ectoderm underlie complete neural tube closure in <i>Xenopus<\/i>"],"prefix":"10.1242","volume":"139","author":[{"given":"Hitoshi","family":"Morita","sequence":"first","affiliation":[{"name":"Division of Morphogenesis, National Institute for Basic Biology, Nishigonaka 38, Myodaiji, Okazaki, Aichi 444-8585, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Kajiura-Kobayashi","sequence":"additional","affiliation":[{"name":"Laboratory for Spatiotemporal Regulations, National Institute for Basic Biology, Nishigonaka 38, Myodaiji, Okazaki, Aichi 444-8585, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiyo","family":"Takagi","sequence":"additional","affiliation":[{"name":"Division of Morphogenesis, National Institute for Basic Biology, Nishigonaka 38, Myodaiji, Okazaki, Aichi 444-8585, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamasa S.","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Morphogenesis, National Institute for Basic Biology, Nishigonaka 38, Myodaiji, Okazaki, Aichi 444-8585, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigenori","family":"Nonaka","sequence":"additional","affiliation":[{"name":"Laboratory for Spatiotemporal Regulations, National Institute for Basic Biology, Nishigonaka 38, Myodaiji, Okazaki, Aichi 444-8585, Japan."},{"name":"Department of Basic Biology, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Shonan Village, Hayama, Kanagawa 240-0193, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Ueno","sequence":"additional","affiliation":[{"name":"Division of Morphogenesis, National Institute for Basic Biology, Nishigonaka 38, Myodaiji, Okazaki, Aichi 444-8585, Japan."},{"name":"Department of Basic Biology, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Shonan Village, Hayama, Kanagawa 240-0193, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042606425104400_R1","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1242\/dev.127.6.1173","article-title":"Endodermal Nodal-related signals and mesoderm induction in Xenopus","volume":"127","author":"Agius","year":"2000","journal-title":"Development"},{"key":"2021042606425104400_R2","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/jez.1402610313","article-title":"Expansion of surface epithelium provides the major extrinsic force for bending of the neural plate","volume":"261","author":"Alvarez","year":"1992","journal-title":"J. Exp. Zool."},{"key":"2021042606425104400_R3","first-page":"393","article-title":"A method for generating transgenic frog embryos","volume":"97","author":"Amaya","year":"1999","journal-title":"Methods Mol. Biol."},{"key":"2021042606425104400_R4","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0012-1606(03)00109-X","article-title":"The function of Xenopus germ cell nuclear factor (xGCNF) in morphogenetic movements during neurulation","volume":"257","author":"Barreto","year":"2003","journal-title":"Dev. Biol."},{"key":"2021042606425104400_R5","doi-asserted-by":"crossref","first-page":"12607","DOI":"10.1073\/pnas.220302597","article-title":"The classical progesterone receptor mediates Xenopus oocyte maturation through a nongenomic mechanism","volume":"97","author":"Bayaa","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042606425104400_R6","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S1534-5807(02)00265-4","article-title":"Integrins in development: moving on, responding to, and sticking to the extracellular matrix","volume":"3","author":"B\u00f6kel","year":"2002","journal-title":"Dev. Cell"},{"key":"2021042606425104400_R7","first-page":"275","article-title":"Neurulation in the Mexican salamander (Ambystoma mexicanum): a drug study and cell shape analysis of the epidermis and the neural plate","volume":"74","author":"Brun","year":"1983","journal-title":"J. Embryol. Exp. Morphol."},{"key":"2021042606425104400_R8","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/0012-1606(71)90073-X","article-title":"Microtubules and microfilaments in newt neuralation","volume":"26","author":"Burnside","year":"1971","journal-title":"Dev. Biol."},{"key":"2021042606425104400_R9","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1093\/icb\/13.4.989","article-title":"Microtubules and microfilaments in amphibian neurulation","volume":"13","author":"Burnside","year":"1973","journal-title":"Am. Zool."},{"key":"2021042606425104400_R10","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ydbio.2005.02.030","article-title":"FGF signal regulates gastrulation cell movements and morphology through its target NRH","volume":"282","author":"Chung","year":"2005","journal-title":"Dev. Biol."},{"key":"2021042606425104400_R11","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/dvdy.1144","article-title":"Towards a cellular and molecular understanding of neurulation","volume":"221","author":"Colas","year":"2001","journal-title":"Dev. Dyn."},{"key":"2021042606425104400_R12","doi-asserted-by":"crossref","first-page":"4547","DOI":"10.1242\/dev.126.20.4547","article-title":"Neural tube closure in Xenopus laevis involves medial migration, directed protrusive activity, cell intercalation and convergent extension","volume":"126","author":"Davidson","year":"1999","journal-title":"Development"},{"key":"2021042606425104400_R13","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1002\/dvdy.20217","article-title":"Assembly and remodeling of the fibrillar fibronectin extracellular matrix during gastrulation and neurulation in Xenopus laevis","volume":"231","author":"Davidson","year":"2004","journal-title":"Dev. Dyn."},{"key":"2021042606425104400_R14","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.cub.2006.03.038","article-title":"Integrin alpha5beta1 and fibronectin regulate polarized cell protrusions required for Xenopus convergence and extension","volume":"16","author":"Davidson","year":"2006","journal-title":"Curr. Biol."},{"key":"2021042606425104400_R15","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1242\/dev.105.1.61","article-title":"A whole-mount immunocytochemical analysis of the expression of the intermediate filament protein vimentin in Xenopus","volume":"105","author":"Dent","year":"1989","journal-title":"Development"},{"key":"2021042606425104400_R16","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1006\/dbio.1997.8711","article-title":"Cellular mechanism underlying neural convergent extension in Xenopus laevis embryos","volume":"191","author":"Elul","year":"1997","journal-title":"Dev. Biol."},{"key":"2021042606425104400_R17","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1002\/dvdy.22099","article-title":"Xenopus Rnd1 and Rnd3 GTP-binding proteins are expressed under the control of segmentation clock and required for somite formation","volume":"238","author":"Goda","year":"2009","journal-title":"Dev. Dyn."},{"key":"2021042606425104400_R18","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/nature02796","article-title":"Planar cell polarity signalling controls cell division orientation during zebrafish gastrulation","volume":"430","author":"Gong","year":"2004","journal-title":"Nature"},{"key":"2021042606425104400_R19","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/(SICI)1097-0177(199712)210:4<397::AID-AJA4>3.0.CO;2-B","article-title":"Epidermal ectoderm is required for full elevation and for convergence during bending of the avian neural plate","volume":"210","author":"Hackett","year":"1997","journal-title":"Dev. Dyn."},{"key":"2021042606425104400_R20","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1242\/dev.127.6.1303","article-title":"Distinct effects of XBF-1 in regulating the cell cycle inhibitor p27(XIC1) and imparting a neural fate","volume":"127","author":"Hardcastle","year":"2000","journal-title":"Development"},{"key":"2021042606425104400_R21","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0091-679X(08)60307-6","article-title":"In situ hybridization: an improved whole-mount method for Xenopus embryos","volume":"36","author":"Harland","year":"1991","journal-title":"Methods Cell Biol."},{"key":"2021042606425104400_R22","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/0896-6273(91)90053-3","article-title":"Neuronal determination without cell division in Xenopus embryos","volume":"6","author":"Harris","year":"1991","journal-title":"Neuron"},{"key":"2021042606425104400_R23","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/jez.1401970205","article-title":"Changes in the shape of the developing vertebrate nervous system analyzed experimentally, mathematically and by computer simulation","volume":"197","author":"Jacobson","year":"1976","journal-title":"J. Exp. Zool."},{"key":"2021042606425104400_R24","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1006\/dbio.1995.1263","article-title":"Tissue boundaries and cell behavior during neurulation","volume":"171","author":"Jacobson","year":"1995","journal-title":"Dev. Biol."},{"key":"2021042606425104400_R25","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1126\/science.1162493","article-title":"Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy","volume":"322","author":"Keller","year":"2008","journal-title":"Science"},{"key":"2021042606425104400_R26","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1126\/science.1079478","article-title":"Shaping the vertebrate body plan by polarized embryonic cell movements","volume":"298","author":"Keller","year":"2002","journal-title":"Science"},{"key":"2021042606425104400_R27","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/0012-1606(76)90127-5","article-title":"Vital dye mapping of the gastrula and neurula of Xenopus laevis. II. Prospective areas and morphogenetic movements of the deep layer","volume":"51","author":"Keller","year":"1976","journal-title":"Dev. Biol."},{"key":"2021042606425104400_R28","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/aja.1001930302","article-title":"The cellular basis of the convergence and extension of the Xenopus neural plate","volume":"193","author":"Keller","year":"1992","journal-title":"Dev. Dyn."},{"key":"2021042606425104400_R29","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1242\/dev.122.10.3173","article-title":"Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation","volume":"122","author":"Kroll","year":"1996","journal-title":"Development"},{"key":"2021042606425104400_R30","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1242\/dev.122.8.2539","article-title":"Integrin alpha 6 expression is required for early nervous system development in Xenopus laevis","volume":"122","author":"Lallier","year":"1996","journal-title":"Development"},{"key":"2021042606425104400_R31","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1242\/dev.02828","article-title":"Shroom family proteins regulate gamma-tubulin distribution and microtubule architecture during epithelial cell shape change","volume":"134","author":"Lee","year":"2007","journal-title":"Development"},{"key":"2021042606425104400_R32","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.cub.2009.12.021","article-title":"Endocytosis is required for efficient apical constriction during Xenopus gastrulation","volume":"20","author":"Lee","year":"2010","journal-title":"Curr. Biol."},{"key":"2021042606425104400_R33","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1242\/dev.043190","article-title":"Nectin-2 and N-cadherin interact through extracellular domains and induce apical accumulation of F-actin in apical constriction of Xenopus neural tube morphogenesis","volume":"137","author":"Morita","year":"2010","journal-title":"Development"},{"key":"2021042606425104400_R34","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nbt0102-87","article-title":"A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applications","volume":"20","author":"Nagai","year":"2002","journal-title":"Nat. Biotechnol."},{"key":"2021042606425104400_R35","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1242\/dev.031203","article-title":"N- and E-cadherins in Xenopus are specifically required in the neural and non-neural ectoderm, respectively, for F-actin assembly and morphogenetic movements","volume":"136","author":"Nandadasa","year":"2009","journal-title":"Development"},{"key":"2021042606425104400_R36","volume-title":"Normal Table of Xenopus laevis (Daudin)","author":"Nieuwkoop","year":"1994"},{"key":"2021042606425104400_R37","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1242\/dev.019646","article-title":"Shroom3-mediated recruitment of Rho kinases to the apical cell junctions regulates epithelial and neuroepithelial planar remodeling","volume":"135","author":"Nishimura","year":"2008","journal-title":"Development"},{"key":"2021042606425104400_R38","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1006\/dbio.1993.1304","article-title":"Integrin expression in early amphibian embryos: cDNA cloning and characterization of Xenopus beta 1, beta 2, beta 3, and beta 6 subunits","volume":"160","author":"Ransom","year":"1993","journal-title":"Dev. Biol."},{"key":"2021042606425104400_R39","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ydbio.2007.12.010","article-title":"Enabled (Xena) regulates neural plate morphogenesis, apical constriction, and cellular adhesion required for neural tube closure in Xenopus","volume":"314","author":"Roffers-Agarwal","year":"2008","journal-title":"Dev. Biol."},{"key":"2021042606425104400_R40","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.ydbio.2008.12.009","article-title":"Morphogenetic movements driving neural tube closure in Xenopus require myosin IIB","volume":"327","author":"Rolo","year":"2009","journal-title":"Dev. Biol."},{"key":"2021042606425104400_R41","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/0092-8674(91)90545-A","article-title":"Ubiquitous MyoD transcription at the midblastula transition precedes induction-dependent MyoD expression in presumptive mesoderm of X. laevis","volume":"65","author":"Rupp","year":"1991","journal-title":"Cell"},{"key":"2021042606425104400_R42","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/aja.1001970405","article-title":"Induction of neuronal differentiation by planar signals in Xenopus embryos","volume":"197","author":"Sater","year":"1993","journal-title":"Dev. Dyn."},{"key":"2021042606425104400_R43","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/(SICI)1096-9861(19970519)381:4<473::AID-CNE7>3.0.CO;2-#","article-title":"Role of nonrandomly oriented cell division in shaping and bending of the neural plate","volume":"381","author":"Sausedo","year":"1997","journal-title":"J. Comp. Neurol."},{"key":"2021042606425104400_R44","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1242\/dev.112.3.713","article-title":"Specification of neurepithelium and surface epithelium in avian transplantation chimeras","volume":"112","author":"Schoenwolf","year":"1991","journal-title":"Development"},{"key":"2021042606425104400_R45","first-page":"427","article-title":"Neurulation in Xenopus laevis. An analysis and model based upon light and electron microscopy","volume":"23","author":"Schroeder","year":"1970","journal-title":"J. Embryol. Exp. Morphol."},{"key":"2021042606425104400_R46","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/S0166-2236(97)01121-1","article-title":"Neurulation: coming to closure","volume":"20","author":"Smith","year":"1997","journal-title":"Trends Neurosci."},{"key":"2021042606425104400_R47","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1242\/dev.02417","article-title":"Radial intercalation of ciliated cells during Xenopus skin development","volume":"133","author":"Stubbs","year":"2006","journal-title":"Development"},{"key":"2021042606425104400_R48","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1046\/j.1440-169X.1995.t01-3-00013.x","article-title":"Bone morphogenetic protein acts as a ventral mesoderm modifier in early Xenopus embryos","volume":"37","author":"Suzuki","year":"1995","journal-title":"Dev. Growth Differ."},{"key":"2021042606425104400_R49","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1242\/dev.048769","article-title":"MID1 and MID2 are required for Xenopus neural tube closure through the regulation of microtubule organization","volume":"137","author":"Suzuki","year":"2010","journal-title":"Development"},{"key":"2021042606425104400_R50","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1126\/science.1157052","article-title":"Apoptotic force and tissue dynamics during Drosophila embryogenesis","volume":"321","author":"Toyama","year":"2008","journal-title":"Science"},{"key":"2021042606425104400_R51","first-page":"15","article-title":"Evidence for a functional role of the cytoskeleton in determination of the dorsoventral axis in Xenopus laevis eggs","volume":"77","author":"Ubbels","year":"1983","journal-title":"J. Embryol. Exp. Morphol."},{"key":"2021042606425104400_R52","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s10439-005-3309-2","article-title":"Multiview robotic microscope reveals the in-plane kinematics of amphibian neurulation","volume":"33","author":"Veldhuis","year":"2005","journal-title":"Ann. Biomed. Eng."},{"key":"2021042606425104400_R53","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1242\/jcs.018564","article-title":"Integrins in cell migration-the actin connection","volume":"122","author":"Vicente-Manzanares","year":"2009","journal-title":"J. Cell Sci."},{"key":"2021042606425104400_R54","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/ajmg.c.30054","article-title":"Neural tube closure and neural tube defects: studies in animal models reveal known knowns and known unknowns","volume":"135C","author":"Wallingford","year":"2005","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"2021042606425104400_R55","doi-asserted-by":"crossref","first-page":"5815","DOI":"10.1242\/dev.00123","article-title":"Neural tube closure requires Dishevelled-dependent convergent extension of the midline","volume":"129","author":"Wallingford","year":"2002","journal-title":"Development"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/139\/8\/1417\/1175271\/1417.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/139\/8\/1417\/1175271\/1417.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T08:59:21Z","timestamp":1619427561000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/139\/8\/1417\/45654\/Cell-movements-of-the-deep-layer-of-non-neural"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4,15]]},"references-count":55,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2012,4,15]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.073239","relation":{},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"value":"1477-9129","type":"electronic"},{"value":"0950-1991","type":"print"}],"subject":[],"published":{"date-parts":[[2012,4,15]]}}}