Shaping mammalian tissues with light : optogenetic control of apical constriction
During embryonic development, cellular forces synchronize in space and time to generate functional tissue shapes. Apical constriction is a force-generating process necessary to provoke the folding of multiple organ primordia during early development. In this thesis, we used a synthetic biology appro...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/675511 |
| Acceso en línea: | http://hdl.handle.net/10803/675511 |
| Access Level: | acceso abierto |
| Palabra clave: | Morphogenesis Optogenetics Epithelial Synthetic Development Morfogenesis Optogenética Epitelial Sintética Desarrollo 576 |
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Shaping mammalian tissues with light : optogenetic control of apical constrictionMartínez Ara, GuillermoMorphogenesisOptogeneticsEpithelialSyntheticDevelopmentMorfogenesisOptogenéticaEpitelialSintéticaDesarrollo576During embryonic development, cellular forces synchronize in space and time to generate functional tissue shapes. Apical constriction is a force-generating process necessary to provoke the folding of multiple organ primordia during early development. In this thesis, we used a synthetic biology approach to engineer control over apical constriction, manipulate morphogenesis and better understand it. We developed “OptoShroom3”, a new optogenetic tool that achieves fast spatiotemporal control of apical constriction in mammalian epithelia. We used OptoShroom3 to manipulate 3D tissue shapes, using light to provoke tissue folding and alter the shape of neural organoids. We further studied the folding of epithelial colonies with 2 different proteins, Shroom3 and Lulu2, and observed that shape biases the direction of folding. Our work pioneers in the use of biological forces to manipulate shape in mammalian tissues. We expect that spatiotemporal control of morphogenesis will promote the study of feedbacks between shape, function and fate.Durante el desarrollo embrionario, las fuerzas celulares se sincronizan para generar tejidos con estructura funcional. La constricción apical es un proceso que provoca el plegamiento de órganos primitivos durante el desarrollo temprano. En esta tesis, hemos usado la biología sintética para controlar la constricción apical, manipular la morfogénesis y entenderla mejor. Hemos desarrollado “OptoShroom3”, un sistema optogenético que permite un rápido control espaciotemporal de la constricción apical en epitelios mamíferos. Hemos usado OptoShroom3 para manipular tejidos 3D, usando la luz para provocar plegamientos y alterar la forma de organoides neurales. Hemos estudiado el plegado de los tejidos epiteliales con dos proteínas diferentes (Shroom3 y Lulu2), observando que la forma original condiciona la dirección del plegado. Este trabajo impulsa el uso de fuerzas biológicas para manipular la forma de los tejidos. Esperamos que el control espaciotemporal de la morfogénesis promueva el estudio de las interacciones entre forma, función y diferenciación.Programa de doctorat en BiomedicinaUniversitat Pompeu FabraEbisuya, MikiUniversitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida202220242022info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion116 p.application/pdfapplication/pdfhttp://hdl.handle.net/10803/675511TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésL'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/6755112026-06-14T12:46:07Z |
| dc.title.none.fl_str_mv |
Shaping mammalian tissues with light : optogenetic control of apical constriction |
| title |
Shaping mammalian tissues with light : optogenetic control of apical constriction |
| spellingShingle |
Shaping mammalian tissues with light : optogenetic control of apical constriction Martínez Ara, Guillermo Morphogenesis Optogenetics Epithelial Synthetic Development Morfogenesis Optogenética Epitelial Sintética Desarrollo 576 |
| title_short |
Shaping mammalian tissues with light : optogenetic control of apical constriction |
| title_full |
Shaping mammalian tissues with light : optogenetic control of apical constriction |
| title_fullStr |
Shaping mammalian tissues with light : optogenetic control of apical constriction |
| title_full_unstemmed |
Shaping mammalian tissues with light : optogenetic control of apical constriction |
| title_sort |
Shaping mammalian tissues with light : optogenetic control of apical constriction |
| dc.creator.none.fl_str_mv |
Martínez Ara, Guillermo |
| author |
Martínez Ara, Guillermo |
| author_facet |
Martínez Ara, Guillermo |
| author_role |
author |
| dc.contributor.none.fl_str_mv |
Ebisuya, Miki Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida |
| dc.subject.none.fl_str_mv |
Morphogenesis Optogenetics Epithelial Synthetic Development Morfogenesis Optogenética Epitelial Sintética Desarrollo 576 |
| topic |
Morphogenesis Optogenetics Epithelial Synthetic Development Morfogenesis Optogenética Epitelial Sintética Desarrollo 576 |
| description |
During embryonic development, cellular forces synchronize in space and time to generate functional tissue shapes. Apical constriction is a force-generating process necessary to provoke the folding of multiple organ primordia during early development. In this thesis, we used a synthetic biology approach to engineer control over apical constriction, manipulate morphogenesis and better understand it. We developed “OptoShroom3”, a new optogenetic tool that achieves fast spatiotemporal control of apical constriction in mammalian epithelia. We used OptoShroom3 to manipulate 3D tissue shapes, using light to provoke tissue folding and alter the shape of neural organoids. We further studied the folding of epithelial colonies with 2 different proteins, Shroom3 and Lulu2, and observed that shape biases the direction of folding. Our work pioneers in the use of biological forces to manipulate shape in mammalian tissues. We expect that spatiotemporal control of morphogenesis will promote the study of feedbacks between shape, function and fate. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2022 2024 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/doctoralThesis info:eu-repo/semantics/publishedVersion |
| format |
doctoralThesis |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10803/675511 |
| url |
http://hdl.handle.net/10803/675511 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.rights.none.fl_str_mv |
http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
http://creativecommons.org/licenses/by/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
116 p. application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Universitat Pompeu Fabra |
| publisher.none.fl_str_mv |
Universitat Pompeu Fabra |
| dc.source.none.fl_str_mv |
TDX (Tesis Doctorals en Xarxa) reponame:TDR. Tesis Doctorales en Red instname:CBUC, CESCA |
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CBUC, CESCA |
| reponame_str |
TDR. Tesis Doctorales en Red |
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TDR. Tesis Doctorales en Red |
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1869405495762092032 |
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15,301603 |