Morphogenesis and mechanics of epithelial tissues
- Uncovering the fundamental cell working principles and the emerging supracellular mechanisms driving epithelial morphogenesis
- Unraveling the biomechanical force fields directing flow and change in shape of epithelial tissues
- Understanding how patterns of gene expression result in tissue shape transformations during embryo development
We are focused in understanding how cellular and sub-cellular properties are integrated at the embryo scale to give rise to emerging mechanisms necessary to drive coordinated tissue flows and remodeling during development. To that end we use the Drosophila melanogaster and the sea urchin Paracentrotus lividus embryos as model systems. The projects developed in the lab gather people from different backgrounds (biology, computer science, physics and engineering) to generate an interdisciplinary and synergistic group in an international environment.
Figure: cell displacement field shown over a Drosophila embryo cylindrical projection. Red indicates faster cell displacement. Ventral in the center, dorsal on the right and left, anterior top and posterior bottom.
From the embryo to the cell and back
Developing embryos are fascinating and powerful platforms to study the biology and physics of cell collective behavior in a physiological relevant context. The research we do in the lab aims to push further the understanding of tissue morphogenesis and the technology necessary to tackle such understanding. We implement cutting edge imaging techniques that can provide a synthetic view of the coordination of tissues at the scale of the embryo with subcellular resolution, laser manipulation, magnetic tweezers, micro-pipetting, optogenetic-based synthetic morphology, big-data processing and multidimensional image analysis. Computational modelling is implemented to delineate a formal physical framework that can theoretically reproduce morphogenetic processes and predict features of the system that are then back tested experimentally.
Figure: gene expression pattern of the dorsal-ventral patterning gene snail (blue) and of the anterior-posterior patterning gene eve (magenta) shown over a Drosophila embryo cylindrical projection. Ventral in the center, dorsal on the right and left, anterior top and posterior bottom.
Tissue folding is a key process during embryo development. Via folding, cells can be translocated in inner region of an embryo where the inside organs will eventually form. We are focused in deciphering the cell mechanisms and the mechanical forces driving epithelial folding during early Drosophila embryo development.
Composite morphogenesis is the process by which a tissue undergoes multiple and simultaneous shape transformations. For instance, during neurulation epithelia extend along the embryo anterior-posterior axis, separating the head from the tail, while simultaneously folding to form the neural tube. How cells can drive multiple and concomitant tissue shape transformations is not well understood. We have discovered that epithelial cells can devise multiple tiers of adherens junctions with specialized functions at different cell apical-basal positions. We aim to uncover the origin of multi-tier junctions responsible for composite morphogenesis.
The formation of epithelial tubes is essential to build organs responsible to direct vital factors outside-in, inside-out or within a living animal (e.g., food and water in gut, air in lungs, saliva from salivary-tubes, blood in blood-vessels etc.). Therefore, tubing plays a critical role in multicellular life where an inside and an outside are established. We aim to uncover the signaling pathways and the cell mechanisms responsible for tube formation. To this end we use the sea urchin gastrula, a powerful model system ideal for in toto embryo analysis and direct measurements of tissue mechanical properties. We study the formation of the gut resulting from multiple coordinated and radially planar polarized cell shape changes.
- Fierling, J, John, A, Delorme, B, Torzynski, A, Blanchard, GB, Lye, CM et al.. Embryo-scale epithelial buckling forms a propagating furrow that initiates gastrulation. Nat Commun. 2022;13 (1):3348. doi: 10.1038/s41467-022-30493-3. PubMed PMID:35688832 PubMed Central PMC9187723.
- John, A, Rauzi, M. Composite morphogenesis during embryo development. Semin Cell Dev Biol. 2021;120 :119-132. doi: 10.1016/j.semcdb.2021.06.007. PubMed PMID:34172395 .
- John, A, Rauzi, M. A two-tier junctional mechanism drives simultaneous tissue folding and extension. Dev Cell. 2021;56 (10):1469-1483.e5. doi: 10.1016/j.devcel.2021.04.003. PubMed PMID:33891900 .
- Popkova, A, Rauzi, M, Wang, X. Cellular and Supracellular Planar Polarity: A Multiscale Cue to Elongate the Drosophila Egg Chamber. Front Cell Dev Biol. 2021;9 :645235. doi: 10.3389/fcell.2021.645235. PubMed PMID:33738289 PubMed Central PMC7961075.
- Rauzi, M. Cell intercalation in a simple epithelium. Philos Trans R Soc Lond B Biol Sci. 2020;375 (1809):20190552. doi: 10.1098/rstb.2019.0552. PubMed PMID:32829682 PubMed Central PMC7482223.
- Popkova, A, Stone, OJ, Chen, L, Qin, X, Liu, C, Liu, J et al.. A Cdc42-mediated supracellular network drives polarized forces and Drosophila egg chamber extension. Nat Commun. 2020;11 (1):1921. doi: 10.1038/s41467-020-15593-2. PubMed PMID:32317641 PubMed Central PMC7174421.
- de Medeiros, G, Kromm, D, Balazs, B, Norlin, N, Günther, S, Izquierdo, E et al.. Cell and tissue manipulation with ultrashort infrared laser pulses in light-sheet microscopy. Sci Rep. 2020;10 (1):1942. doi: 10.1038/s41598-019-54349-x. PubMed PMID:32029815 PubMed Central PMC7005178.
- Rauzi, M, Krzic, U, Saunders, TE, Krajnc, M, Ziherl, P, Hufnagel, L et al.. Embryo-scale tissue mechanics during Drosophila gastrulation movements. Nat Commun. 2015;6 :8677. doi: 10.1038/ncomms9677. PubMed PMID:26497898 PubMed Central PMC4846315.
- Collinet, C, Rauzi, M, Lenne, PF, Lecuit, T. Local and tissue-scale forces drive oriented junction growth during tissue extension. Nat Cell Biol. 2015;17 (10):1247-58. doi: 10.1038/ncb3226. PubMed PMID:26389664 .
- Bajoghli, B, Kuri, P, Inoue, D, Aghaallaei, N, Hanelt, M, Thumberger, T et al.. Noninvasive In Toto Imaging of the Thymus Reveals Heterogeneous Migratory Behavior of Developing T Cells. J Immunol. 2015;195 (5):2177-86. doi: 10.4049/jimmunol.1500361. PubMed PMID:26188059 .
- Rauzi, M, Hočevar Brezavšček, A, Ziherl, P, Leptin, M. Physical models of mesoderm invagination in Drosophila embryo. Biophys J. 2013;105 (1):3-10. doi: 10.1016/j.bpj.2013.05.039. PubMed PMID:23823218 PubMed Central PMC3699736.
- Hočevar Brezavšček, A, Rauzi, M, Leptin, M, Ziherl, P. A model of epithelial invagination driven by collective mechanics of identical cells. Biophys J. 2012;103 (5):1069-77. doi: 10.1016/j.bpj.2012.07.018. PubMed PMID:23009857 PubMed Central PMC3433605.
- Rauzi, M, Lenne, PF. Cortical forces in cell shape changes and tissue morphogenesis. Curr Top Dev Biol. 2011;95 :93-144. doi: 10.1016/B978-0-12-385065-2.00004-9. PubMed PMID:21501750 .
- Rauzi, M, Lenne, PF, Lecuit, T. Planar polarized actomyosin contractile flows control epithelial junction remodelling. Nature. 2010;468 (7327):1110-4. doi: 10.1038/nature09566. PubMed PMID:21068726 .
- Bertet, C, Rauzi, M, Lecuit, T. Repression of Wasp by JAK/STAT signalling inhibits medial actomyosin network assembly and apical cell constriction in intercalating epithelial cells. Development. 2009;136 (24):4199-212. doi: 10.1242/dev.040402. PubMed PMID:19934015 .
- Rauzi, M, Lecuit, T. Closing in on mechanisms of tissue morphogenesis. Cell. 2009;137 (7):1183-5. doi: 10.1016/j.cell.2009.06.009. PubMed PMID:19563750 .
- Rauzi, M, Verant, P, Lecuit, T, Lenne, PF. Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis. Nat Cell Biol. 2008;10 (12):1401-10. doi: 10.1038/ncb1798. PubMed PMID:18978783 .
- Cavey, M, Rauzi, M, Lenne, PF, Lecuit, T. A two-tiered mechanism for stabilization and immobilization of E-cadherin. Nature. 2008;453 (7196):751-6. doi: 10.1038/nature06953. PubMed PMID:18480755 .
- Rauzi M. Probing tissue interaction with laser-based cauterization in the early developing Drosophila embryo. Methods Cell Biol. 2017;139:153-165. doi: 10.1016/bs.mcb.2016.11.003. Epub 2016 Dec 23. PMID: 28215334.
- Rauzi M, Lenne PF. Probing cell mechanics with subcellular laser dissection of actomyosin networks in the early developing Drosophila embryo. Methods Mol Biol. 2015;1189:209-18. doi: 10.1007/978-1-4939-1164-6_14. PMID: 25245696.
Inserm biology technician position at the Université Côte d’Azur
We are seeking a talented and motivated candidate with a Bachelor Degree +2 in biotechnology (for instance graduated from a IUT) for a technician position to work in the teams of Dr. Matteo RAUZI and Dr. Arnaud HUBSTIENBERGER at the Institut de Biologie Valrose (University Côte d’Azur). This job offer can eventually result in a permanent position.
Tasks to be fulfilled:
- Learning and conducting genetic crosses for both the Drosphila and Elegans model systems.
- Learning and applying confocal microscopy imaging techniques on fixed and living
- Conducting molecular biology and biochemical
- Preparing solutions and media for the members of the
- Helping the members of the teams in their
- Taking care of the orders for consumables and small
- Taking care of the safety
- Fostering cohesiveness among the people in the lab.
- Mastery of the English language
- Maintaining a lab notebook
- Team spirit
Interdisciplinary Doctoral project
at the interface between engineering, biology, physics and informatics
at the University Côte d’Azur
Studying the mechanisms and mechanics driving epithelial tube formation
The formation of epithelial tubes is essential to build organs responsible to direct vital factors outside-in, inside-out or within a living animal (e.g., food and water in gut, air in lungs, saliva from salivary-tubes, blood in blood-vessels etc.). Therefore, tubing plays a critical role in multicellular life organized in stratified layers (i.e., where an inside and an outside is established). Understanding the mechanisms and mechanics responsible for tube formation is thus of great importance. Tube formation can result from tissue in-pocketing. The mechanisms responsible for in-pocketing are not well understood. To dissect and study this process, we use the sea urchin gastrula: a quite simple (i.e., powerful) model system ideal for in vivo mechanical studies. Our preliminary data highlight a possible combination of coordinated and radially planar cell polarized mechanisms that could be responsible for simultaneous uniaxial folding and extension of the vegetal plate. By implementing infra-red femtosecond ablation coupled to 4D multi-view light sheet microscopy, drug and RNAi perturbation, µ-aspiration and indentation to measure tissue mechanical properties, in toto 4D segmentation and mathematical modelling, this work will shine new light on the mechanisms and mechanics driving tissue in-pocketing for tube formation.
The project will be developped in the Rauzi lab that gathers people from different backgrounds (biology, informatics, physics, and engineering) to generate an interdisciplinary and synergistic group in an international environment.
We are seeking a motivated and talanted candidate to develop this PhD project.
Send by the 12th of May 2021 a CV, a motivation letter, master scores/ranking and reference letters to firstname.lastname@example.org
RAUZI LAB: http://ibv.unice.fr/research-team/rauzi/
2017 - HFSP CDA
2017 - ATIP-Avenir
2016 - ANR T-ERC
2012 - HFSP Long Term Fellowship
2011 - Embo-Marie Curie Long Term Fellowship
iBV - Institut de Biologie Valrose
Université Nice Sophia Antipolis
Faculté des Sciences
06108 Nice cedex 2