Project title: Study of the epithelial connectivity during the intestinal development.
Type of rotation: M2 (6 months)
Supervisors: Delphine Delacour
Concept and Objectives
Epithelia act as a physical barrier against external aggressions but also ensure organ functionality. If not correctly assembled or dysfunctional, this leads to pathological situations that include a variety of diseases spanning from rare developmental syndromes or cancer. How epithelia coordinate and harmonize the responses of each cell with not only their nearest neighbors, but entire tissue, to guarantee proper spatial arrangement, integrity and functionality is still not well understood. The intestinal epithelium is a tremendous model for this field of research, as it is one of the most fast-proliferative and regenerative in mammalian organisms. However, the study of the cellular and developmental mechanisms that govern the development and architecture of the intestinal tissue is still in its infancy. The general objective of our team focuses on understanding the determination and maintenance of intestinal functional domains, and to evaluate their spatiotemporal coordination. One of the strong aspects of our research is to confront in vivo and in vitro murine and human disease models, and to combine different approaches from advanced cell biology, tissue engineering, histology, molecular biology and biophysics.
The master project (M2) aims at characterizing the epithelial connectivity and collective behavior of the intestinal differentiated domain in homeostatic conditions or under challenging contexts. During his master internship, the student will combine ex vivo intestinal organoid cultures, and in vivo analyses with intestines from mice to reveal morphogenetic mechanisms that sustain epithelial coordination. For that purpose, the student will use diverse techniques: 2D and 3D organoid cultures, mouse dissection, live microscopy, molecular biology and image analysis.
References
1) Saleh J, Fardin MA, Barai A, Soleilhac M, Frenoy O, Gaston C, Ciu H, Dang T, Gaudin N, Vincent A, Minc N and Delacour D. Length-limitation of astral microtubules orients cell divisions in intestinal crypts. Developmental Cell (2023), https://doi.org/10.1016/j.devcel.2023.06.004 BioRXiv doi: https://doi.org/10.1101/2022.09.02.506333
2) Guevara A, Soleilhac M, Minc N and Delacour D. Regulation and functions of cell division in the intestinal tissue. Seminars in Cell and Developmental Biology (2023), S1084-9521(23)00004-6.
3) Xi W, Saleh J, Yamada A, Mercier B, Dang T, Janel S, Soleilhac M, Wu H, Tomba C, Romagnolo B, Lafont F, Mège RM, Chen Y and Delacour D. Modulation of designer biomimetic matrices for optimized intestinal epithelial cultures. Biomaterials (2022), 282:121380.
4) Gaston C, De Beco S, Doss B, Pan M, Gauquelin E, D’Alessandro J, Lim CT, Ladoux B and Delacour D. Spatio-temporal modulation of cortical RhoA zone conditions epithelial organization. Nature Communications, (2021), 12:2226.
5) Salomon J, Gaston C, Magescas J, Duvauchelle B, Campeotto F, Canioni D, Sengmanivong L, Mayeux A, Michaux G, Poirier F, Minc N, Schmitz J, Brousse N, Ladoux B, Goulet O and Delacour D. Contractile forces at tricellular contacts modulate epithelial organization and monolayer integrity. Nature Communications (2017), 8:13998.