Open AccessCell fate coordinates mechano-osmotic forces in intestinal crypt formation
Author(s) -
Qiutan Yang,
Shi-Lei Xue,
Chii Jou Chan,
Markus Rempfler,
Dario Vischi,
Francisca Maurer-Gutierrez,
Takashi Hiiragi,
Édouard Hannezo,
Prisca Liberali
Publication year - 2021
Publication title -
nature cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 11.38
H-Index - 369
eISSN - 1476-4679
pISSN - 1465-7392
DOI - 10.1038/s41556-021-00700-2
Subject(s) - crypt , morphogenesis , microbiology and biotechnology , organoid , lumen (anatomy) , biology , live cell imaging , biophysics , chemistry , cell , anatomy , biochemistry , endocrinology , gene
Intestinal organoids derived from single cells undergo complex crypt-villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. Here, using light-sheet microscopy and large-scale imaging quantification, we demonstrate that crypt formation coincides with a stark reduction in lumen volume. We develop a 3D biophysical model to computationally screen different mechanical scenarios of crypt morphogenesis. Combining this with live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven crypt apical contraction and villus basal tension work synergistically with lumen volume reduction to drive crypt morphogenesis, and demonstrate the existence of a critical point in differential tensions above which crypt morphology becomes robust to volume changes. Finally, we identified a sodium/glucose cotransporter that is specific to differentiated enterocytes that modulates lumen volume reduction through cell swelling in the villus region. Together, our study uncovers the cellular basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust morphogenesis.