Shaping mammalian tissues with light : optogenetic control of apical constriction

Martínez Ara, Guillermo

Shaping mammalian tissues with light : optogenetic control of apical constriction

Document Type

Doctoral thesis
Published Version

Author

Martínez Ara, Guillermo

Director

Ebisuya, Miki

Publication Date

2022-09-19

Pages

116 p.

License

Citation

Martínez Ara, G. Shaping mammalian tissues with light : optogenetic control of apical constriction. Universitat Pompeu Fabra; 2022. handle: http://hdl.handle.net/10803/675511

This citation was generated automatically.

Doctoral program

Programa de doctorat en Biomedicina

Abstract

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.
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.