{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:35:18Z","timestamp":1773534918077,"version":"3.50.1"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T00:00:00Z","timestamp":1464048000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T00:00:00Z","timestamp":1464048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cadherin switching from E-cadherin (E-cad) to N-cadherin (N-cad) is a key step of the epithelial-mesenchymal transition (EMT) processes that occurs during gastrulation and cancer progression. We investigate whether cadherins actively participate in progression of EMT by crosstalk to signaling pathways. We apply ectopic cadherin switching before the onset of mouse gastrulation. Mutants with an induced E-cad to N-cad switch (Ncadki) die around E8.5. Severe morphological changes including a small epiblast, a rounded shape, an enlarged extra-embryonic compartment and lack of the amnion, combined with a massive cell detachment from the ectodermal layer are detected. In contrast to epiblast-specific E-cad depletion, gastrulation is initiated in Ncadki embryos, but patterning of the germ-layers is abnormal. An overall reduction in BMP signaling, expansion of<jats:italic>Nodal<\/jats:italic>and<jats:italic>Eomes<\/jats:italic>domains, combined with reduced<jats:italic>Wnt3a<\/jats:italic>expression at the primitive streak is observed. Our results show that in addition to cadherin-dependent adhesion, proper embryonic development requires E-cad mediated signaling function to facilitate a feedback loop that stabilizes<jats:italic>Bmp4<\/jats:italic>and<jats:italic>Bmp2<\/jats:italic>expression in the extraembryonic ectoderm and sustained downstream activity in the epiblast. Moreover, for proper morphogenesis a fine-tuned spatio-temporal control of cadherin switching is required during EMT at gastrulation to avoid premature cell detachment and migration.<\/jats:p>","DOI":"10.1038\/srep26562","type":"journal-article","created":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T16:50:02Z","timestamp":1464108602000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Inappropriate cadherin switching in the mouse epiblast compromises proper signaling between the epiblast and the extraembryonic ectoderm during gastrulation"],"prefix":"10.1038","volume":"6","author":[{"given":"M. Felicia","family":"Basilicata","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Frank","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davor","family":"Solter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Brabletz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc P.","family":"Stemmler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,5,24]]},"reference":[{"key":"BFsrep26562_CR1","doi-asserted-by":"publisher","first-page":"8263","DOI":"10.1073\/pnas.91.17.8263","volume":"91","author":"L Larue","year":"1994","unstructured":"Larue, L., Ohsugi, M., Hirchenhain, J. & Kemler, R. E-cadherin null mutant embryos fail to form a trophectoderm epithelium. Proc Natl Acad Sci. USA 91, 8263\u20138267 (1994).","journal-title":"Proc Natl Acad Sci. USA"},{"key":"BFsrep26562_CR2","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1242\/dev.02722","volume":"134","author":"NG Kan","year":"2007","unstructured":"Kan, N. G. et al. Gene replacement reveals a specific role for E-cadherin in the formation of a functional trophectoderm. Development 134, 31\u201341 (2007).","journal-title":"Development"},{"key":"BFsrep26562_CR3","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/S0925-4773(02)00090-4","volume":"115","author":"O Boussadia","year":"2002","unstructured":"Boussadia, O., Kutsch, S., Hierholzer, A., Delmas, V. & Kemler, R. E-cadherin is a survival factor for the lactating mouse mammary gland. Mech Dev 115, 53\u201362 (2002).","journal-title":"Mech Dev"},{"key":"BFsrep26562_CR4","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1038\/sj.emboj.7600605","volume":"24","author":"JA Tunggal","year":"2005","unstructured":"Tunggal, J. A. et al. E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions. Embo Journal 24, 1146\u20131156 (2005).","journal-title":"Embo Journal"},{"key":"BFsrep26562_CR5","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1006\/dbio.1996.8443","volume":"181","author":"GL Radice","year":"1997","unstructured":"Radice, G. L. et al. Developmental defects in mouse embryos lacking N-cadherin. Developmental biology 181, 64\u201378 (1997).","journal-title":"Developmental biology"},{"key":"BFsrep26562_CR6","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1002\/stem.134","volume":"27","author":"F Soncin","year":"2009","unstructured":"Soncin, F. et al. Abrogation of E-cadherin-mediated cell-cell contact in mouse embryonic stem cells results in reversible LIF-independent self-renewal. Stem Cells 27, 2069\u20132080 (2009).","journal-title":"Stem Cells"},{"key":"BFsrep26562_CR7","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1242\/dev.088690","volume":"140","author":"I del Valle","year":"2013","unstructured":"del Valle, I. et al. E-cadherin is required for the proper activation of the Lifr\/Gp130 signaling pathway in mouse embryonic stem cells. Development 140, 1684\u20131692 (2013).","journal-title":"Development"},{"key":"BFsrep26562_CR8","doi-asserted-by":"publisher","first-page":"e1002609","DOI":"10.1371\/journal.pgen.1002609","volume":"8","author":"I Bedzhov","year":"2012","unstructured":"Bedzhov, I., Liszewska, E., Kanzler, B. & Stemmler, M. P. Igf1r signaling is indispensable for preimplantation development and is activated via a novel function of E-cadherin. PLoS Genet 8, e1002609 (2012).","journal-title":"PLoS Genet"},{"key":"BFsrep26562_CR9","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/0896-6273(94)90027-2","volume":"13","author":"EJ Williams","year":"1994","unstructured":"Williams, E. J., Furness, J., Walsh, F. S. & Doherty, P. Activation of the FGF receptor underlies neurite outgrowth stimulated by L1, N-CAM, and N-cadherin. Neuron 13, 583\u2013594 (1994).","journal-title":"Neuron"},{"key":"BFsrep26562_CR10","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/S1535-6108(02)00150-2","volume":"2","author":"K Suyama","year":"2002","unstructured":"Suyama, K., Shapiro, I., Guttman, M. & Hazan, R. B. A signaling pathway leading to metastasis is controlled by N-cadherin and the FGF receptor. Cancer Cell 2, 301\u2013314 (2002).","journal-title":"Cancer Cell"},{"key":"BFsrep26562_CR11","doi-asserted-by":"publisher","first-page":"35208","DOI":"10.1074\/jbc.M608655200","volume":"281","author":"E Sanchez-Heras","year":"2006","unstructured":"Sanchez-Heras, E., Howell, F. V., Williams, G. & Doherty, P. The fibroblast growth factor receptor acid box is essential for interactions with N-cadherin and all of the major isoforms of neural cell adhesion molecule. J Biol Chem 281, 35208\u201335216 (2006).","journal-title":"J Biol Chem"},{"key":"BFsrep26562_CR12","doi-asserted-by":"publisher","first-page":"3411","DOI":"10.1038\/onc.2013.310","volume":"33","author":"X Qian","year":"2014","unstructured":"Qian, X. et al. N-cadherin\/FGFR promotes metastasis through epithelial-to-mesenchymal transition and stem\/progenitor cell-like properties. Oncogene 33, 3411\u20133421 (2014).","journal-title":"Oncogene"},{"key":"BFsrep26562_CR13","doi-asserted-by":"publisher","first-page":"41227","DOI":"10.1074\/jbc.M006578200","volume":"275","author":"S Pece","year":"2000","unstructured":"Pece, S. & Gutkind, J. S. Signaling from E-cadherins to the MAPK pathway by the recruitment and activation of epidermal growth factor receptors upon cell-cell contact formation. J Biol Chem 275, 41227\u201341233 (2000).","journal-title":"J Biol Chem"},{"key":"BFsrep26562_CR14","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1158\/0008-5472.CAN-07-1588","volume":"68","author":"A Bremm","year":"2008","unstructured":"Bremm, A. et al. Enhanced activation of epidermal growth factor receptor caused by tumor-derived E-cadherin mutations. Cancer Res 68, 707\u2013714 (2008).","journal-title":"Cancer Res"},{"key":"BFsrep26562_CR15","doi-asserted-by":"publisher","first-page":"8184","DOI":"10.1128\/MCB.21.23.8184-8188.2001","volume":"21","author":"EA Carver","year":"2001","unstructured":"Carver, E. A., Jiang, R., Lan, Y., Oram, K. F. & Gridley, T. The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition. Mol Cell Biol 21, 8184\u20138188 (2001).","journal-title":"Mol Cell Biol"},{"key":"BFsrep26562_CR16","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1146\/annurev-cellbio-092910-154036","volume":"27","author":"MA Nieto","year":"2011","unstructured":"Nieto, M. A. The ins and outs of the epithelial to mesenchymal transition in health and disease. Annu Rev Cell Dev Biol 27, 347\u2013376 (2011).","journal-title":"Annu Rev Cell Dev Biol"},{"key":"BFsrep26562_CR17","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/S0925-4773(02)00292-7","volume":"2","author":"S Hayashi","year":"2002","unstructured":"Hayashi, S., Lewis, P., Pevny, L. & McMahon, A. P. Efficient gene modulation in mouse epiblast using a Sox2Cre transgenic mouse strain. Gene Expr Patterns 2, 93\u201397 (2002).","journal-title":"Gene Expr Patterns"},{"key":"BFsrep26562_CR18","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1242\/dev.129.10.2367","volume":"129","author":"M Kanai-Azuma","year":"2002","unstructured":"Kanai-Azuma, M. et al. Depletion of definitive gut endoderm in Sox17-null mutant mice. Development 129, 2367\u20132379 (2002).","journal-title":"Development"},{"key":"BFsrep26562_CR19","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1002\/dvg.20829","volume":"50","author":"I Burtscher","year":"2012","unstructured":"Burtscher, I., Barkey, W., Schwarzfischer, M., Theis, F. J. & Lickert, H. The Sox17-mCherry fusion mouse line allows visualization of endoderm and vascular endothelial development. Genesis 50, 496\u2013505 (2012).","journal-title":"Genesis"},{"key":"BFsrep26562_CR20","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1038\/ncb3070","volume":"16","author":"M Viotti","year":"2014","unstructured":"Viotti, M., Nowotschin, S. & Hadjantonakis, A. K. SOX17 links gut endoderm morphogenesis and germ layer segregation. Nat Cell Biol 16, 1146\u20131156 (2014).","journal-title":"Nat Cell Biol"},{"key":"BFsrep26562_CR21","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/j.devcel.2008.07.017","volume":"15","author":"GS Kwon","year":"2008","unstructured":"Kwon, G. S., Viotti, M. & Hadjantonakis, A. K. The endoderm of the mouse embryo arises by dynamic widespread intercalation of embryonic and extraembryonic lineages. Dev Cell 15, 509\u2013520 (2008).","journal-title":"Dev Cell"},{"key":"BFsrep26562_CR22","doi-asserted-by":"publisher","first-page":"3081","DOI":"10.1038\/nprot.2007.418","volume":"2","author":"K Takahashi","year":"2007","unstructured":"Takahashi, K., Okita, K., Nakagawa, M. & Yamanaka, S. Induction of pluripotent stem cells from fibroblast cultures. Nat Protoc 2, 3081\u20133089 (2007).","journal-title":"Nat Protoc"},{"key":"BFsrep26562_CR23","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/1479-5876-4-20","volume":"4","author":"N Tanaka","year":"2006","unstructured":"Tanaka, N., Takeuchi, T., Neri, Q. V., Sills, E. S. & Palermo, G. D. Laser-assisted blastocyst dissection and subsequent cultivation of embryonic stem cells in a serum\/cell free culture system: applications and preliminary results in a murine model. J Transl Med 4, 20 (2006).","journal-title":"J Transl Med"},{"key":"BFsrep26562_CR24","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/nrg1827","volume":"7","author":"D Solter","year":"2006","unstructured":"Solter, D. From teratocarcinomas to embryonic stem cells and beyond: a history of embryonic stem cell research. Nat Rev Genet 7, 319\u2013327 (2006).","journal-title":"Nat Rev Genet"},{"key":"BFsrep26562_CR25","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1016\/j.scr.2013.08.009","volume":"11","author":"I Bedzhov","year":"2013","unstructured":"Bedzhov, I. et al. Adhesion, but not a specific cadherin code, is indispensable for ES cell and induced pluripotency. Stem Cell Res 11, 1250\u20131263 (2013).","journal-title":"Stem Cell Res"},{"key":"BFsrep26562_CR26","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1016\/S0960-9822(03)00433-0","volume":"13","author":"M Marsden","year":"2003","unstructured":"Marsden, M. & DeSimone, D. W. Integrin-ECM interactions regulate cadherin-dependent cell adhesion and are required for convergent extension in Xenopus. Curr Biol 13, 1182\u20131191 (2003).","journal-title":"Curr Biol"},{"key":"BFsrep26562_CR27","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1242\/jcs.100115","volume":"126","author":"M Canel","year":"2013","unstructured":"Canel, M., Serrels, A., Frame, M. C. & Brunton, V. G. E-cadherin-integrin crosstalk in cancer invasion and metastasis. Journal of cell science 126, 393\u2013401 (2013).","journal-title":"Journal of cell science"},{"key":"BFsrep26562_CR28","doi-asserted-by":"publisher","first-page":"13324","DOI":"10.1073\/pnas.1002662107","volume":"107","author":"N Borghi","year":"2010","unstructured":"Borghi, N., Lowndes, M., Maruthamuthu, V., Gardel, M. L. & Nelson, W. J. Regulation of cell motile behavior by crosstalk between cadherin- and integrin-mediated adhesions. Proc Natl Acad Sci. USA 107, 13324\u201313329 (2010).","journal-title":"Proc Natl Acad Sci. USA"},{"key":"BFsrep26562_CR29","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1242\/dev.118.3.829","volume":"118","author":"CA Burdsal","year":"1993","unstructured":"Burdsal, C. A., Damsky, C. H. & Pedersen, R. A. The role of E-cadherin and integrins in mesoderm differentiation and migration at the mammalian primitive streak. Development 118, 829\u2013844 (1993).","journal-title":"Development"},{"key":"BFsrep26562_CR30","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1242\/dev.122.10.2977","volume":"122","author":"H Zhang","year":"1996","unstructured":"Zhang, H. & Bradley, A. Mice deficient for BMP2 are nonviable and have defects in amnion\/chorion and cardiac development. Development 122, 2977\u20132986 (1996).","journal-title":"Development"},{"key":"BFsrep26562_CR31","doi-asserted-by":"publisher","first-page":"3343","DOI":"10.1242\/dev.075465","volume":"139","author":"PN Pereira","year":"2012","unstructured":"Pereira, P. N. et al. Antagonism of Nodal signaling by BMP\/Smad5 prevents ectopic primitive streak formation in the mouse amnion. Development 139, 3343\u20133354 (2012).","journal-title":"Development"},{"key":"BFsrep26562_CR32","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1101\/gad.9.17.2105","volume":"9","author":"G Winnier","year":"1995","unstructured":"Winnier, G., Blessing, M., Labosky, P. A. & Hogan, B. L. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes & development 9, 2105\u20132116 (1995).","journal-title":"Genes & development"},{"key":"BFsrep26562_CR33","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1101\/gad.13.4.424","volume":"13","author":"KA Lawson","year":"1999","unstructured":"Lawson, K. A. et al. Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes & development 13, 424\u2013436 (1999).","journal-title":"Genes & development"},{"key":"BFsrep26562_CR34","doi-asserted-by":"publisher","first-page":"13739","DOI":"10.1073\/pnas.241508898","volume":"98","author":"T Fujiwara","year":"2001","unstructured":"Fujiwara, T., Dunn, N. R. & Hogan, B. L. Bone morphogenetic protein 4 in the extraembryonic mesoderm is required for allantois development and the localization and survival of primordial germ cells in the mouse. Proc Natl Acad Sci. USA 98, 13739\u201313744 (2001).","journal-title":"Proc Natl Acad Sci. USA"},{"key":"BFsrep26562_CR35","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1111\/j.1440-169X.2008.01059.x","volume":"50","author":"ML Soares","year":"2008","unstructured":"Soares, M. L., Torres-Padilla, M. E. & Zernicka-Goetz, M. Bone morphogenetic protein 4 signaling regulates development of the anterior visceral endoderm in the mouse embryo. Dev Growth Differ 50, 615\u2013621 (2008).","journal-title":"Dev Growth Differ"},{"key":"BFsrep26562_CR36","doi-asserted-by":"publisher","first-page":"e86691","DOI":"10.1371\/journal.pone.0086691","volume":"9","author":"A Raggioli","year":"2014","unstructured":"Raggioli, A., Junghans, D., Rudloff, S. & Kemler, R. Beta-catenin is vital for the integrity of mouse embryonic stem cells. PLoS One 9, e86691 (2014).","journal-title":"PLoS One"},{"key":"BFsrep26562_CR37","doi-asserted-by":"publisher","first-page":"3767","DOI":"10.1242\/dev.02552","volume":"133","author":"S Miura","year":"2006","unstructured":"Miura, S., Davis, S., Klingensmith, J. & Mishina, Y. BMP signaling in the epiblast is required for proper recruitment of the prospective paraxial mesoderm and development of the somites. Development 133, 3767\u20133775 (2006).","journal-title":"Development"},{"key":"BFsrep26562_CR38","doi-asserted-by":"publisher","first-page":"2330","DOI":"10.1002\/dvdy.22375","volume":"239","author":"MP Stemmler","year":"2010","unstructured":"Stemmler, M. P. & Bedzhov, I. A Cdh1HA knock-in allele rescues the Cdh1\u2212\/\u2212 phenotype but shows essential Cdh1 function during placentation. Developmental dynamics: an official publication of the American Association of Anatomists 239, 2330\u20132344 (2010).","journal-title":"Developmental dynamics: an official publication of the American Association of Anatomists"},{"key":"BFsrep26562_CR39","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1242\/dev.048488","volume":"137","author":"L Libusova","year":"2010","unstructured":"Libusova, L., Stemmler, M. P., Hierholzer, A., Schwarz, H. & Kemler, R. N-cadherin can structurally substitute for E-cadherin during intestinal development but leads to polyp formation. Development 137, 2297\u20132305 (2010).","journal-title":"Development"},{"key":"BFsrep26562_CR40","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nrm2618","volume":"10","author":"SJ Arnold","year":"2009","unstructured":"Arnold, S. J. & Robertson, E. J. Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo. Nature reviews. Molecular cell biology 10, 91\u2013103 (2009).","journal-title":"Nature reviews. Molecular cell biology"},{"key":"BFsrep26562_CR41","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1242\/dev.120.7.1919","volume":"120","author":"FL Conlon","year":"1994","unstructured":"Conlon, F. L. et al. A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse. Development 120, 1919\u20131928 (1994).","journal-title":"Development"},{"key":"BFsrep26562_CR42","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1101\/gad.12.6.844","volume":"12","author":"Z Gu","year":"1998","unstructured":"Gu, Z. et al. The type I activin receptor ActRIB is required for egg cylinder organization and gastrulation in the mouse. Genes & development 12, 844\u2013857 (1998).","journal-title":"Genes & development"},{"key":"BFsrep26562_CR43","doi-asserted-by":"publisher","first-page":"3027","DOI":"10.1101\/gad.9.24.3027","volume":"9","author":"Y Mishina","year":"1995","unstructured":"Mishina, Y., Suzuki, A., Ueno, N. & Behringer, R. R. Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis. Genes & development 9, 3027\u20133037 (1995).","journal-title":"Genes & development"},{"key":"BFsrep26562_CR44","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.ydbio.2010.02.038","volume":"341","author":"S Miura","year":"2010","unstructured":"Miura, S., Singh, A. P. & Mishina, Y. Bmpr1a is required for proper migration of the AVE through regulation of Dkk1 expression in the pre-streak mouse embryo. Developmental biology 341, 246\u2013254 (2010).","journal-title":"Developmental biology"},{"key":"BFsrep26562_CR45","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1242\/dev.02742","volume":"134","author":"I Shoval","year":"2007","unstructured":"Shoval, I., Ludwig, A. & Kalcheim, C. Antagonistic roles of full-length N-cadherin and its soluble BMP cleavage product in neural crest delamination. Development 134, 491\u2013501 (2007).","journal-title":"Development"},{"key":"BFsrep26562_CR46","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.cell.2003.08.008","volume":"114","author":"P Marambaud","year":"2003","unstructured":"Marambaud, P. et al. A CBP binding transcriptional repressor produced by the PS1\/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell 114, 635\u2013645 (2003).","journal-title":"Cell"},{"key":"BFsrep26562_CR47","doi-asserted-by":"publisher","first-page":"e01197","DOI":"10.7554\/eLife.01197","volume":"2","author":"M Malaguti","year":"2013","unstructured":"Malaguti, M. et al. Bone morphogenic protein signalling suppresses differentiation of pluripotent cells by maintaining expression of E-Cadherin. Elife 2, e01197 (2013).","journal-title":"Elife"},{"key":"BFsrep26562_CR48","doi-asserted-by":"publisher","first-page":"2691","DOI":"10.1242\/dev.050096","volume":"137","author":"KS Park","year":"2010","unstructured":"Park, K. S. & Gumbiner, B. M. Cadherin 6B induces BMP signaling and de-epithelialization during the epithelial mesenchymal transition of the neural crest. Development 137, 2691\u20132701 (2010).","journal-title":"Development"},{"key":"BFsrep26562_CR49","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1038\/5007","volume":"21","author":"P Soriano","year":"1999","unstructured":"Soriano, P. Generalized lacZ expression with the ROSA26 Cre reporter strain. Nature genetics 21, 70\u201371 (1999).","journal-title":"Nature genetics"},{"key":"BFsrep26562_CR50","unstructured":"Damjanov, I., Damjanov, A. & Solter, D. Production of teratocarcinomas from embryos transplanted to extra-uterine sites, in Teratocarcinomas and embryonic stem cells: a practical approach. (ed. E. J. Robertson ) 1\u201318 (IRL Press, Oxford; Washington, D.C; 1987)."},{"key":"BFsrep26562_CR51","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/dvdy.22075","volume":"239","author":"A Hierholzer","year":"2010","unstructured":"Hierholzer, A. & Kemler, R. Beta-catenin-mediated signaling and cell adhesion in postgastrulation mouse embryos. Developmental dynamics: an official publication of the American Association of Anatomists 239, 191\u2013199 (2010).","journal-title":"Developmental dynamics: an official publication of the American Association of Anatomists"},{"key":"BFsrep26562_CR52","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/978-1-60761-691-7_2","volume":"636","author":"JG Chenoweth","year":"2010","unstructured":"Chenoweth, J. G. & Tesar, P. J. Isolation and maintenance of mouse epiblast stem cells. Methods in molecular biology 636, 25\u201344 (2010).","journal-title":"Methods in molecular biology"},{"key":"BFsrep26562_CR53","doi-asserted-by":"publisher","first-page":"3355","DOI":"10.1093\/brain\/aws254","volume":"135","author":"L Tonges","year":"2012","unstructured":"Tonges, L. et al. Inhibition of rho kinase enhances survival of dopaminergic neurons and attenuates axonal loss in a mouse model of Parkinson\u2019s disease. Brain 135, 3355\u20133370 (2012).","journal-title":"Brain"},{"key":"BFsrep26562_CR54","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.ydbio.2010.04.020","volume":"344","author":"DM Messerschmidt","year":"2010","unstructured":"Messerschmidt, D. M. & Kemler, R. Nanog is required for primitive endoderm formation through a non-cell autonomous mechanism. Developmental biology 344, 129\u2013137 (2010).","journal-title":"Developmental biology"},{"key":"BFsrep26562_CR55","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/0014-4827(84)90241-6","volume":"152","author":"D Vestweber","year":"1984","unstructured":"Vestweber, D. & Kemler, R. Rabbit antiserum against a purified surface glycoprotein decompacts mouse preimplantation embryos and reacts with specific adult tissues. Experimental cell research 152, 169\u2013178 (1984).","journal-title":"Experimental cell research"},{"key":"BFsrep26562_CR56","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1006\/dbio.1997.8560","volume":"185","author":"M Ohsugi","year":"1997","unstructured":"Ohsugi, M., Larue, L., Schwarz, H. & Kemler, R. Cell-junctional and cytoskeletal organization in mouse blastocysts lacking E-cadherin. Developmental biology 185, 261\u2013271 (1997).","journal-title":"Developmental biology"},{"key":"BFsrep26562_CR57","unstructured":"Boller, K. & Kemler, R. In vitro differentiation of embryonal carcinoma cells characterized by monoclonal antibodies against embryonic cell markers, In Teratocarcinoma stem cells, Cold Spring Harbor conferences on cell proliferation. (eds L. M. Silver, G. R. Martin & S. Strickland ) 39\u201349 (Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y; 1983)."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep26562.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep26562","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep26562.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T02:52:07Z","timestamp":1718592727000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep26562"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,24]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,5,31]]}},"alternative-id":["BFsrep26562"],"URL":"https:\/\/doi.org\/10.1038\/srep26562","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,24]]},"assertion":[{"value":"14 January 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26562"}}