{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:14:55Z","timestamp":1772172895668,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009063","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000}}],"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/M01021X\/1"],"award-info":[{"award-number":["BB\/M01021X\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/M012522\/1"],"award-info":[{"award-number":["BB\/M012522\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/M011151\/1"],"award-info":[{"award-number":["BB\/M011151\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000287","name":"Royal Academy of Engineering","doi-asserted-by":"crossref","award":["CiET1819\\19"],"award-info":[{"award-number":["CiET1819\\19"]}],"id":[{"id":"10.13039\/501100000287","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/N026993\/1"],"award-info":[{"award-number":["EP\/N026993\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    A common feature of morphogenesis is the formation of three-dimensional structures from the folding of two-dimensional epithelial sheets, aided by cell shape changes at the cellular-level. Changes in cell shape must be studied in the context of cell-polarised biomechanical processes within the epithelial sheet. In epithelia with highly curved surfaces, finding single-cell alignment along a biological axis can be difficult to automate\n                    <jats:italic>in silico<\/jats:italic>\n                    . We present \u2018Origami\u2019, a MATLAB-based image analysis pipeline to compute direction-variant cell shape features along the epithelial apico-basal axis. Our automated method accurately computed direction vectors denoting the apico-basal axis in regions with opposing curvature in synthetic epithelia and fluorescence images of zebrafish embryos. As proof of concept, we identified different cell shape signatures in the developing zebrafish inner ear, where the epithelium deforms in opposite orientations to form different structures. Origami is designed to be user-friendly and is generally applicable to fluorescence images of curved epithelia.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1009063","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T13:35:29Z","timestamp":1635773729000},"page":"e1009063","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Origami: Single-cell 3D shape dynamics oriented along the apico-basal axis of folding epithelia from fluorescence microscopy data"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6232-4970","authenticated-orcid":true,"given":"Tania","family":"Mendonca","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9602-4917","authenticated-orcid":true,"given":"Ana A.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0759-3510","authenticated-orcid":true,"given":"Jose M.","family":"Pozo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6760-9457","authenticated-orcid":true,"given":"Sarah","family":"Baxendale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1575-1504","authenticated-orcid":true,"given":"Tanya T.","family":"Whitfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2675-528X","authenticated-orcid":true,"given":"Alejandro F.","family":"Frangi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"pcbi.1009063.ref001","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1242\/dev.112.2.365","article-title":"Drosophila gastrulation: analysis of cell shape changes in living embryos by three-dimensional fluorescence microscopy","volume":"112","author":"Z Kam","year":"1991","journal-title":"Development (Cambridge, England)."},{"key":"pcbi.1009063.ref002","first-page":"47","volume-title":"Seminars in Cell and Developmental Biology","author":"B Alsina","year":"2017"},{"key":"pcbi.1009063.ref003","first-page":"1","article-title":"Differential lateral and basal tension drive folding of Drosophila wing discs through two distinct mechanisms","volume":"9","author":"L Sui","year":"2018","journal-title":"Nature Communications"},{"key":"pcbi.1009063.ref004","first-page":"82","volume-title":"Trends in Cell Biology","author":"LA Davidson","year":"2012"},{"key":"pcbi.1009063.ref005","doi-asserted-by":"crossref","first-page":"20150526","DOI":"10.1098\/rstb.2015.0526","article-title":"Cellular systems for epithelial invagination.","volume":"372","author":"EJ Pearl","year":"2017","journal-title":"Philosophical Transactions of the Royal Society B: Biological Sciences."},{"key":"pcbi.1009063.ref006","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1126\/science.1100035","article-title":"Optical Sectioning Deep Inside Live Embryos by Selective Plane Illumination Microscopy","volume":"305","author":"J Huisken","year":"2004","journal-title":"Science"},{"key":"pcbi.1009063.ref007","doi-asserted-by":"crossref","first-page":"e64506","DOI":"10.1371\/journal.pone.0064506","article-title":"Live Imaging of Whole Mouse Embryos during Gastrulation: Migration Analyses of Epiblast and Mesodermal Cells.","volume":"8","author":"T Ichikawa","year":"2013","journal-title":"PLoS ONE"},{"key":"pcbi.1009063.ref008","doi-asserted-by":"crossref","first-page":"143826","DOI":"10.7554\/eLife.37131","article-title":"Lamellar projections in the endolymphatic sac act as a relief valve to regulate inner ear pressure.","volume":"7","author":"IA Swinburne","year":"2018","journal-title":"eLife"},{"key":"pcbi.1009063.ref009","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1242\/dev.045872","article-title":"Cytoskeletal dynamics and supracellular organisation of cell shape fluctuations during dorsal closure","volume":"137","author":"GB Blanchard","year":"2010","journal-title":"Development (Cambridge, England)"},{"key":"pcbi.1009063.ref010","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.devcel.2015.12.012","article-title":"EpiTools: An Open-Source Image Analysis Toolkit for Quantifying Epithelial Growth Dynamics","volume":"36","author":"D Heller","year":"2016","journal-title":"Developmental Cell"},{"key":"pcbi.1009063.ref011","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1242\/dev.146837","article-title":"SEGGA: a toolset for rapid automated analysis of epithelial cell polarity and dynamics","volume":"144","author":"DL Farrell","year":"2017","journal-title":"Development"},{"key":"pcbi.1009063.ref012","doi-asserted-by":"crossref","first-page":"032401","DOI":"10.1103\/PhysRevE.95.032401","article-title":"Triangles bridge the scales: Quantifying cellular contributions to tissue deformation","volume":"95","author":"M Merkel","year":"2017","journal-title":"Physical Review E"},{"key":"pcbi.1009063.ref013","doi-asserted-by":"crossref","first-page":"e35717","DOI":"10.7554\/eLife.35717","article-title":"Radially-patterned cell behaviours during tube budding from an epithelium","volume":"7","author":"YE Sanchez-Corrales","year":"2018","journal-title":"eLife"},{"key":"pcbi.1009063.ref014","doi-asserted-by":"crossref","first-page":"e1002780","DOI":"10.1371\/journal.pcbi.1002780","article-title":"ACME: Automated Cell Morphology Extractor for Comprehensive Reconstruction of Cell Membranes.","volume":"8","author":"KR Mosaliganti","year":"2012","journal-title":"PLoS Computational Biology"},{"key":"pcbi.1009063.ref015","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.devcel.2015.12.028","article-title":"Real-Time Three-Dimensional Cell Segmentation in Large-Scale Microscopy Data of Developing Embryos","volume":"36","author":"J Stegmaier","year":"2016","journal-title":"Developmental cell"},{"key":"pcbi.1009063.ref016","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s12859-019-2720-x","article-title":"3DMMS: Robust 3D Membrane Morphological Segmentation of C. elegans embryo","volume":"20","author":"J Cao","year":"2019","journal-title":"BMC Bioinformatics"},{"key":"pcbi.1009063.ref017","doi-asserted-by":"crossref","first-page":"e2005970","DOI":"10.1371\/journal.pbio.2005970","article-title":"CellProfiler 3.0: Next-generation image processing for biology. Misteli T, editor","volume":"16","author":"C McQuin","year":"2018","journal-title":"PLOS Biology"},{"key":"pcbi.1009063.ref018","first-page":"223","article-title":"Choudhury RC, Meyerowitz E, Cunha A, Stegmaier J. CNN-based preprocessing to optimize watershed-based cell segmentation in 3d confocal microscopy images. Proceedings\u2014International Symposium on Biomedical Imaging","author":"D Eschweiler","year":"2019","journal-title":"IEEE Computer Society"},{"key":"pcbi.1009063.ref019","first-page":"147","article-title":"EPySeg: a coding-free solution for automated segmentation of epithelia using deep learning","author":"B Aigouy","year":"2020","journal-title":"Development"},{"key":"pcbi.1009063.ref020","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41592-020-01018-x","article-title":"Cellpose: a generalist algorithm for cellular segmentation","volume":"18","author":"C Stringer","year":"2021","journal-title":"Nature Methods"},{"key":"pcbi.1009063.ref021","first-page":"1","article-title":"Establishment of a morphological atlas of the Caenorhabditis elegans embryo using deep-learning-based 4D segmentation","volume":"11","author":"J Cao","year":"2020","journal-title":"Nature Communications"},{"key":"pcbi.1009063.ref022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.05864","article-title":"MorphoGraphX: A platform for quantifying morphogenesis in 4D.","volume":"4","author":"P Barbier de Reuille","year":"2015","journal-title":"eLife"},{"key":"pcbi.1009063.ref023","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ydbio.2020.02.003","article-title":"ShapeMetrics: A userfriendly pipeline for 3D cell segmentation and spatial tissue analysis","volume":"462","author":"H Takko","year":"2020","journal-title":"Developmental Biology"},{"key":"pcbi.1009063.ref024","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1242\/dev.110.1.73","article-title":"Cell shape changes during gastrulation in Drosophila","volume":"110","author":"M Leptin","year":"1990","journal-title":"Development (Cambridge, England)."},{"key":"pcbi.1009063.ref025","doi-asserted-by":"crossref","first-page":"5177","DOI":"10.1242\/dev.067868","article-title":"A trio-rhoA-shroom3 pathway is required for apical constriction and epithelial invagination","volume":"138","author":"TF Plageman","year":"2011","journal-title":"Development"},{"key":"pcbi.1009063.ref026","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.15797","article-title":"Analysis of cellular behavior and cytoskeletal dynamics reveal a constriction mechanism driving optic cup morphogenesis.","volume":"5","author":"M Nicol\u00e1s-P\u00e9rez","year":"2016","journal-title":"eLife"},{"key":"pcbi.1009063.ref027","article-title":"Orchestrating morphogenesis: building the body plan by cell shape changes and movements","author":"KZ Perez-Vale","year":"2020","journal-title":"Development (Cambridge, England). NLM (Medline)"},{"key":"pcbi.1009063.ref028","first-page":"1","volume-title":"Current Opinion in Genetics and Development","author":"G Gillard","year":"2020"},{"key":"pcbi.1009063.ref029","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1242\/dev.087940","article-title":"Quantitative analysis of polarity in 3D reveals local cell coordination in the embryonic mouse heart","volume":"140","author":"JF Le Garrec","year":"2013","journal-title":"Development (Cambridge)"},{"key":"pcbi.1009063.ref030","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nature14152","article-title":"Apico-basal forces exerted by apoptotic cells drive epithelium folding","volume":"518","author":"B Monier","year":"2015","journal-title":"Nature"},{"key":"pcbi.1009063.ref031","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.55913","article-title":"An image-based data-driven analysis of cellular architecture in a developing tissue.","volume":"9","author":"J Hartmann","year":"2020","journal-title":"eLife"},{"key":"pcbi.1009063.ref032","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.cell.2014.09.007","article-title":"Interplay of cell shape and division orientation promotes robust morphogenesis of developing epithelia","volume":"159","author":"F Xiong","year":"2014","journal-title":"Cell"},{"key":"pcbi.1009063.ref033","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1242\/dev.107730","article-title":"Quantitative 4D analyses of epithelial folding during Drosophila gastrulation.","volume":"141","author":"Z Khan","year":"2014","journal-title":"Development (Cambridge)"},{"key":"pcbi.1009063.ref034","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2019.09.016","article-title":"LongAxis: A MATLAB-based program for 3D quantitative analysis of epithelial cell shape and orientation","volume":"458","author":"KR Carney","year":"2020","journal-title":"Developmental Biology"},{"key":"pcbi.1009063.ref035","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1109\/TPAMI.2010.139","article-title":"Efficient 3D Geometric and Zernike Moments Computation from Unstructured Surface Meshes","volume":"33","author":"JM Pozo","year":"2011","journal-title":"IEEE Transactions on Pattern Analysis and Machine Intelligence"},{"key":"pcbi.1009063.ref036","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1145\/280814.280947","volume-title":"Proceedings of the 25th annual conference on Computer graphics and interactive techniques\u2014SIGGRAPH \u201898","author":"N Amenta","year":"1998"},{"key":"pcbi.1009063.ref037","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/PL00009475","article-title":"Surface reconstruction by Voronoi filtering","volume":"22","author":"N Amenta","year":"1999","journal-title":"Discrete and Computational Geometry"},{"key":"pcbi.1009063.ref038","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1109\/2945.817351","article-title":"The ball-pivoting algorithm for surface reconstruction","volume":"5","author":"F Bernardini","year":"1999","journal-title":"IEEE Transactions on Visualization and Computer Graphics"},{"key":"pcbi.1009063.ref039","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.cad.2011.02.012","article-title":"A new mesh-growing algorithm for fast surface reconstruction","volume":"43","author":"L Di Angelo","year":"2011","journal-title":"CAD Computer Aided Design"},{"key":"pcbi.1009063.ref040","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/ar.1092100113","article-title":"Epithelial fusion during early semicircular canal formation in the embryonic zebrafish,Brachydanio rerio","volume":"210","author":"RE Waterman","year":"1984","journal-title":"The Anatomical Record"},{"key":"pcbi.1009063.ref041","article-title":"Moment Functions in Image Analysis\u2014Theory and Applications. Moment Functions in Image Analysis\u2014Theory and Applications.","author":"R Mukundan","year":"1998","journal-title":"WORLD SCIENTIFIC"},{"key":"pcbi.1009063.ref042","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1109\/TMI.2007.901008","article-title":"Morphological characterization of intracranial aneurysms using 3-D moment invariants","volume":"26","author":"RD Mill\u00e1n","year":"2007","journal-title":"IEEE Transactions on Medical Imaging"},{"key":"pcbi.1009063.ref043","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.cmpb.2013.06.005","article-title":"Comparison of organs\u2019 shapes with geometric and Zernike 3D moments","volume":"111","author":"D Broggio","year":"2013","journal-title":"Computer Methods and Programs in Biomedicine"},{"key":"pcbi.1009063.ref044","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1086\/623964","article-title":"Volume, Shape, and Roundness of Rock Particles","volume":"40","author":"H Wadell","year":"1932","journal-title":"The Journal of Geology"},{"key":"pcbi.1009063.ref045","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1242\/dev.034215","article-title":"Nkcc1 (Slc12a2) is required for the regulation of endolymph volume in the otic vesicle and swim bladder volume in the zebrafish larva.","volume":"136","author":"L Abbas","year":"2009","journal-title":"Development"},{"key":"pcbi.1009063.ref046","doi-asserted-by":"crossref","first-page":"4362","DOI":"10.1242\/dev.098061","article-title":"Semicircular canal morphogenesis in the zebrafish inner ear requires the function of gpr126 (lauscher), an adhesion class G protein-coupled receptor gene.","volume":"140","author":"FS Geng","year":"2013","journal-title":"Development (Cambridge)"},{"issue":"5","key":"pcbi.1009063.ref047","first-page":"53","article-title":"Analysis of Multivariate Data and Repeated Measures Designs with the R Package MANOVA.RM.","volume":"37","author":"S Friedrich","year":"2018","journal-title":"Family Medicine"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1009063","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1009063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T13:46:33Z","timestamp":1636638393000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1009063"}},"subtitle":[],"editor":[{"given":"Dina","family":"Schneidman-Duhovny","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,11,1]]},"references-count":47,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1009063","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.05.13.443974","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,1]]}}}