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This is characterised in flat epithelial layers, where average neighbour distributions follow conserved arrangements. However, less is known about how curvature defines tissue architecture. Epithelial shells constitute a critical structural stage in early mammalian embryonic development. Our analysis reveals how the closed, curved geometry of epithelial shells limits their 3D organisation. Here, we designed computational models that predict shell surface topology across different cell numbers. To validate the model, MDCK cysts with precise cell\u2010level segmentation were analysed. Our results show that more pentagons are required to accommodate higher curvature per cell patch, a restriction also observed in early mouse embryos. Small cysts and embryos exhibited a restricted subset of polygon configurations, predominantly those maximising the area\u2010to\u2010perimeter ratio. We conclude that epithelial shells are organised under general rules mirroring other natural cages, revealing that geometric and curvature constraints guide early epithelial organisation.<\/jats:p>","DOI":"10.1002\/advs.77487","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T10:41:19Z","timestamp":1790592079000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Interplay of Curvature, Geometry, and Topology Shapes Tissue Organisation in Epithelial Shells"],"prefix":"10.1002","author":[{"given":"Laura","family":"Morato","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla Departamento de Biolog\u00eda Celular Facultad de Biolog\u00eda Universidad de Sevilla  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas A.","family":"Andr\u00e9s\u2010San Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla Departamento de Biolog\u00eda Celular Facultad de Biolog\u00eda Universidad de Sevilla  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Garrido\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla Departamento de Matem\u00e1tica Aplicada I Universidad de Sevilla  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Gordillo\u2010V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla Departamento de Biolog\u00eda Celular Facultad de Biolog\u00eda Universidad de Sevilla  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"Palacios","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla Departamento de Biolog\u00eda Celular Facultad de Biolog\u00eda Universidad de Sevilla  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Lidue\u00f1a\u2010Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla Departamento de Biolog\u00eda Celular Facultad de Biolog\u00eda Universidad de Sevilla  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"McDole","sequence":"additional","affiliation":[{"name":"MRC Laboratory of Molecular Biology  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0509-227X","authenticated-orcid":false,"given":"Pedro","family":"G\u00f3mez\u2010G\u00e1lvez","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla Departamento de Biolog\u00eda Celular Facultad de Biolog\u00eda Universidad de Sevilla  Seville Spain"},{"name":"Biomedical Network Research Centre on Neurodegenerative Diseases (CIBERNED)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Annese","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla Departamento de Biolog\u00eda Celular Facultad de Biolog\u00eda Universidad de Sevilla  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8030-1820","authenticated-orcid":false,"given":"Luis M.","family":"Escudero","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla Departamento de Biolog\u00eda Celular Facultad de Biolog\u00eda Universidad de Sevilla  Seville Spain"},{"name":"Biomedical Network Research Centre on Neurodegenerative Diseases (CIBERNED)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Developmental Biology","author":"Gilbert S. 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