Morphogenesis and mechanics of epithelial tissues
- Tissue mechanics
- Bridging scales from cell to the embryo to understand morphogenesis during development
- Live imaging, quantitative biology, mechanical and genetic manipulation
From cell mechanics to embryo morphogenesis
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 tissue remodeling during development. The projects developed in the lab gather people from different backgrounds (biology, informatics, physics, and engineering) to generate an interdisciplinary and synergistic group in an international environment.
Developmental biology is a field of great interest since it allows studying cells in a physiological relevant context. That is why scientists have been considering the embryo as an interesting “environment” in which to analyze and learn more about the biology and physics of cells. While much work has been done in dissecting cellular and subcellular properties, little is known of how nano and micro scale mechanisms are integrated at the embryo and how emerging properties arise to drive coordinated tissue flows and tissue remodeling responsable for morphogenesis and impacting on cell fate determination. The research we do aims to bridge scales from the subcellular to the embryo. This represents the ultimate understanding of how an embryo changes its shape during development.
The research we do in the lab aims to push further both the understanding of embryo development and the technology necessary to tackle such understanding. We use and develop cutting edge imaging techniques, laser manipulation, magnetic tweezers, optogenetic-based synthetic morphology, and image analysis with systematic BIG data processing. The study is done comparatively on wild type and mutated embryos. in silico 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.
Tissue fold formation is a common morphological process taking place during morphogenesis. Such a process plays a key role in embryo development since it allows translocating cells in inner zones of the embryo where specific organs of the mature animal will then originate (process named gastrulation).
A model system that is particularly suited for studying folding is for example the Drosophila embryo for which many genetic tools are available and several manipulation tools can be applied to probe cell mechanics. In the early Drosophila embryo it has been shown that a tissue can fold via different mechanisms.
How can a tissue, during fold formation, change its curvature from convex to concave?
How are forces distributed in time at the surface and in the bulk of the embryo to drive morphogenesis?
Finally, how do tissue mechanics and morphogenesis impact on EMT, cell migration and cell fate determination?
- 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.
DOCTORAL POSITION AT THE UNIVERSITY CÔTE D’AZUR
4D MORPHOMETRIC STUDY OF CELL AND TISSUE SHAPE CHANGES TO COMPUTATIONALLY
UNRAVEL THE PROCESS OF SEA URCHIN EMBRYO GASTRULATION
Computational morphometric analysis has become an essential tool in modern biology to better understand how cell and tissue change shape during embryo development. Therefore, exciting collaborations among computer scientists and biologists have arisen to pierce the mystery of how life take shape. In recent years, new microscopy techniques (e.g., SPIM) have enabled the digital image acquisition of developing embryos with unprecedented 3D spatial and temporal resolution allowing a fine reconstruction of all the morphogenetic processes concurring to shape the embryo .
The acquisition of 3D+t high resolved image series results in huge amount of data (also referred to as BIG data sets). Basic image processing approaches fail to provide the necessary tools for multi-dimensional image analysis. We have developed sophisticated image analysis tools to extract multi-dimensional information from BIG data sets . Our image analysis tools were successfully applied to embryos constituted of tens of cells . Very recently, in a joint collaboration between the Morpheme team and the Rauzi team, this computational tool has been extended to temporal 3D image series of the developing sea urchin embryo constituted by more than 1000 cells. These BIG data sets together with our image analysis tools give access for the first time to detailed morphometric information of shape changes of each single cell (tracked over time in 3D) forming the sea urchin embryo .
We are at present interested in better understating the mechanisms driving gastrulation in the sea urchin embryo. During this developmental phase, the tissue located at the vegetal pole buckles initiating gut formation. Such changes in tissue shape are driven by stereotypic cell shape and topological changes. The goal of this doctoral project is to characterize in 4D the cell shape/topology and cytoskeletal protein variations, and to perform cell population analysis to eventually unveil the key stereotypic processes driving tissue buckling.
We are seeking a very motivated and talented candidate with advanced expertise in computer science, mathematics or physics. We expect the candidate to have skills in several of the following fields: Image Processing and Analysis, Data Sciences, and Machine Learning. S/he should be proficient in programming in C/C++ and Python languages. Previous experience in biological or medical imaging will be considered as an asset.
Applicants must send as soon as possible a CV, a statement of interest, and 2 or 3 reference letters to Grégoire Malandain (firstname.lastname@example.org) and to Matteo Rauzi (email@example.com).
Deadline: 17th of May 2020
Location: Inria-I3S Morpheme team, I3S, Sophia-Antipolis, France
 PJ Keller, “Imaging Morphogenesis: Technological Advances and Biological Insights,” Science, vol. 340, no. 6137, pp. 1234168+, June 2013.
 R Fernandez, P Das, V Mirabet, E Moscardi, J Traas, JL Verdeil, G Malandain, and C Godin, “Imaging plant growth in 4-d: robust tissue reconstruction and lineaging at cell resolution,”Nat Meth, vol. 7, pp. 547–553, 2010.
 Guignard, L., Fiuza, U.-M., Leggio, B., Laussu, J., Faure, E., Michelin, G., Biasuz, K., Hufnagel, L., Malandain, G., Godin, C., and Lemaire, P. (2020). Contact-area dependent cell communications and the morphological invariance of ascidian embryogenesis. Science, accepted for publication.
 Moullet, A. (2020) “Automated segmentation of sea urchin embryos”, Ms thesis.
Doctoral position at the Côte d’Azur & Sorbonne University
Studying the molecular control and the mechanics of sea urchin gastrulation: a model for epithelial folding
Epithelial folding is a key process in the life of all animals. During embryogenesis, this process takes place notably during gastrulation. In the laboratory, we use the sea urchin embryo to study the mechanisms, mechanics and molecular control of epithelial folding. Sea urchin gastrulae combine a number of outstanding features making this model system a unique opportunity to study folding: (i) external development and tissue simplicity enabling both experimentation and modeling approaches; (ii) cell transparency allowing in toto light sheet imaging; (iii) known key signaling factors and available methods for functional analyses; and (iv) mechanically accessible tissues permitting direct measurements of tissue mechanical properties. Given these features, the sea urchin gastrula is thus a perfect playground for both biologists and biophysicists. The aim is to provide new insights on the fundamental process of epithelial folding both at the mechanical and molecular levels.
The proposed project is a collaborative work between two laboratories (Rauzi M. at iBV in Nice and Croce J. at the LBDV at the marine station in Villefranche-sur-Mer) that gather people from different backgrounds (biology, informatics, physics, and engineering) to generate an interdisciplinary and synergistic group in an international environment.
Seeking a talented and very motivated candidate.
Deadline: April 27th, 2020. Starting date: October 2020.
Send as soon as possible a CV, a motivation letter, master scores/ranking and reference letters to: firstname.lastname@example.org and email@example.com
CROCE EVOINSIDE / RAUZI LAB
Postdoctoral position at the University Côte d’Azur
Studying the mechanisms and mechanics of sea urchin gastrulation: a model for epithelial folding
During embryo gastrulation one of the key morphogenetic processes is tissue folding. We use the sea urchin embryo, a spherical monolayer epithelium that folds its vegetal plate forming a tube: the future gut. What are the mechanisms and the mechanical foces driving folding is still not well understood.The sea urchin gastrula combines a number of outstanding features making this model system a unique opportunity to study the mechanisms and mechanics of tissue folding: (1) simplicity; (2) transparencey for in toto light sheet imaging; (3) known key signaling factors; (4) the gastrula is a mechanically accessible tissue: it can be partitioned, cells can be transplanted, micro-indentation and micro-pipetting techniques can be applied to measure tissue mechanical properties. The sea urchin gastrula is thus a perfect playground for biologists and biophysicists.
The projects developed in the lab gather people from different backgrounds (biology, informatics, physics, and engineering) to generate an interdisciplinary and synergistic group in an international environment.
Seeking talanted candidates preferibly with expereince in micro pipetting, nano/μ indentation, live imaging, light sheet microscopy or marine model systems.
Deadline: May 10th, 2020. Starting date: Before the end of 2020.
Send a CV, motivation letter 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