Matteo RAUZI

Morphogenesis and mechanics of epithelial tissues

Main interests

  • 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

Scientific Questions

Morphogenesis builds living shapes. The change in shape of a cell is controlled by molecular signals and it is driven by mechanical forces powered by the cell cytoskeleton. Therefore, cell shape changes rely on the transfer and conversion of biochemical and mechanical energy. While key molecular players, signaling pathways and the cellular mechanics have been tested and deciphered, it is still unclear how these work at larger spatial scales. In our lab we are focused on understanding how cellular and sub-cellular properties are integrated at the embryo scale to give rise to conserved emerging mechanisms necessary to drive coordinated tissue flows and remodeling during development. To that end we apply a spectrum of cutting edge imaging, molecular and biophysical techniques and tools to tackle morphogenesis from the molecule to the embryo.

Figure: 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.

Our Strategy

From the molecule to the embryo and back

The research we do in the lab aims to push forward the understanding of tissue morphogenesis and to advance the technology necessary to tackle such understanding. Developing embryos are fascinating and powerful platforms to study the biology and physics of cell collective behavior in a physiological relevant context. In the lab we use and compare two powerful model systems: the protostome Drosophila melanogaster and the deuterostome sea urchin Paracentrotus lividus embryos. While Drosophila provides the most advanced genetic tools, the sea urchin embryo is an ideal system to directly probe cell and tissue mechanics. We implement cutting edge imaging techniques that can provide a comprehensive view of the coordination of tissues at the scale of the embryo with subcellular resolution, laser manipulation, 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. 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.

Research Aims

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 known. 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.

Epithelial tubes play a critical role in multicellular life that is organized in stratified layers and in which an inside and an outside are established. The formation of tubes is essential to build organs responsible to direct vital factors outside-in, inside-out as well as within animals (e.g., food and water through the gut, air through the lungs, electrical signals via the spinal cord, and blood in blood-vessels). Therefore, unveiling the mechanisms responsible for tube formation is key to understand the emergence of complex life forms and to decipher how tubulogenesis disorders, that result from tube formation failure (e.g., spina bifida, polycystic kidney, tracheal atresia), may emerge. To study the formation of epithelial tubes, we use the sea urchin gastrula and focus on the formation of the gut emerging from multiple coordinated and radially planar polarized cell shape changes.

Morphogenetic waves result from the propagation of cell and tissue shape changes across an epithelium. A morphogenetic wave is a shape transformation mode that may be energetically efficient and robust to insure a spatio-temporally continuous tissue shape change resulting in a smooth and coherent structure or organ. Epithelial furrows are often the result of a morphogenetic wave that powers the propagation of a fold along a line resulting in a continuous and linear groove. How fold formation and propagation are initiated, driven and controlled is still poorly understood. To shed new light on the key principles governing morphogenetic waves, we study the molecular mechanisms and the mechanics controlling and driving the formation and the propagation of the ventral and of the cephalic furrow during early Drosophila gastrulation.


DELORME Barthélemy - +33 489150861


JALLON Antoine - +33 R
TANARI Abdul Basith - +33 489150866
ROBY Nicolas - +33 489150861

Engineers & Technicians

ROUQUET Sami - +33 489150866
ROUQUET Sami - +33 489150866
AIT MOUFFOK Amel - +33 489150861


HARRATHI Wafa - +33 R
GUEYE Mansour - +33 R


Recent Publications

  1. Popkova, A, Andrenšek, U, Pagnotta, S, Ziherl, P, Krajnc, M, Rauzi, M et al.. A mechanical wave travels along a genetic guide to drive the formation of an epithelial furrow during Drosophila gastrulation. Dev Cell. 2024;59 (3):400-414.e5. doi: 10.1016/j.devcel.2023.12.016. PubMed PMID:38228140 .
  2. 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.
  3. 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 .
  4. 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 .
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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 .
  11. 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 .
  12. 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.
  13. 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.
  14. 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 .
  15. 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 .
  16. 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 .
  17. 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 .
  18. 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 .
  19. 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 .
  20. 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.
  21. 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.
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Master2 internship: interdisciplinary project at the interface between live microscopy, developmental biology, biophysics and image analysis

Studying the mechanisms and mechaincs of epithelial tube formation in the sea urchin P. lividus embryo

Epithelial folding is a vital process during embryo development. Defects in folding can impair neurulation or gastrulation leading to major birth defects (e.g., spina bifida) or death. In mature tissues, folding is also pathologically relevant: tissues can for instance buckle before cancer invasion. Understanding the cell mechanisms and mechanics of tissue folding is thus of major importance. In the lab we use the Paracentrotus lividus sea urchin embryo as a model system and focus on the process of tissue folding during sea urchin gastrulation that leads to the formation of the gut of the sea urchin larva. By implementing 4D multi-view light sheet microscopy, micro-indentation, micro-pipette aspiration, infra-red femtosecond ablation to perturb the cytoskeleton and molecular inhibition, this work will shine new light on the cell mechanisms of epithelial folding at both the molecular and mechanical level.

Novelty of the project. The sea urchin is historically among the first model systems used to study embryo development. 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) the sea urchin gastrula is a 1000 cells spherical monolayer epithelium: a very simple thus appealing model for experimentation and modelling; (2) tissue folding can be nicely imaged since the sea urchin gastrula is transparent; (3) the signaling factors controlling sea urchin vegetal plate folding are known and can be knocked down to dissect their function; (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 on both tissue apical and basal side. The sea urchin gastrula is thus a perfect playground for biologists and biophysicists focus in understanding the mechanisms and mechanics controlling and driving tissue morphogenesis.

The project that we propose is a breakthrough in the study of epithelial folding using the P. lividus model organism. We are now able, by using the sea urchin gastrula, to extract 3D quantitative cell morphology information with sub-cellular resolution. We devised a fluorescent live imaging and processing pipeline that allows to (1) image reliably the gastrulation of the sea urchin embryo in 4D with 200 nm isotropic resolution at a frequency of 1 image/min, (2) segment all 1000 cells constituting the gastrula in 3D and (3) track the 3D segmented cells over time. In this way we can extract precise morphological and cinematic information and use them to rule out or advance hypotheses supporting potential mechanisms driving vegetal plate folding. Hypothesis are tested by using advanced 4D image processing and analysis, mechano- techniques (e.g., in-plane micro-indentation, infra-red (IR) femtosecond (fs) laser dissection coupled to multi- view light-sheet microscopy) and back tested theoretically with mathematical modelling.

Seeking a talanted and very motivated candidate to work on 4D live imaging, molecular biology and biophysics. Send a CV, a motivation letter, master scores/ranking and reference letters to matteo.rauzi@univ-cotedazur.fr

/ Job Offers, Open, RAUZI

Interdisciplinary Doctoral project in the RAUZI lab (University Côte d’Azur, IBV, Nice) and in the ETIENNE lab (Univ Grenoble Alpes, LIPHY, Grenoble), at the interface between computational physics and biology

Studying the mechanisms and mechanics driving tissue folding

Mophogenesis builds living shapes. A key morphogenetic transformation that shapes tissues and organs is epithelial invagination: a tissue bends and it is eventually internalized transforming the physiological topology of the system. The invagination of epithelial tissues is a vital transformation during embryo development since it is pivotal during embryo gastrulation and neurulation. While much is known of the mechanisms and mechanics driving epithelial flattening (first phase) and bending (second phase), how a tissue is eventually internalized (third phase) is still poorly understood. To tackle this, we propose to use the Drosophila embryo that provides the most advanced genetic tools and study the process of mesoderm internalization. On the computational physics side, we will develop a formal physical framework that can theoretically reproduce morphogenetic processes and predict features of the system that are then back tested experimentally. More specifically, we will design a mechanical model based on active viscoelastic shells and use numerical simulations based on existing tools (e.g., Surface Evolver in 3D) to calculate shell deformations. On the biology side, we will implement multi-view light sheet microscopy coupled to optogenetics and plasma-based laser ablation and image data analysis to characterize and synthetically modulate tissue shape changes to test numerical predictions. The student will be trained on these multiple approaches and techniques to develop an interdisciplinary project focused on uncovering the fundamental principles governing epithelial folding. This knowledge could be used in the future to synthetically build and shape functional organs.The project will be developed in both the Rauzi lab (http://ibv.unice.fr/research-team/rauzi/) and the Etienne lab (http://www-liphy.univ-grenoble-alpes.fr/pagesperso/etienne).

We are seeking a highly motivated and talented candidate to develop this interdisciplinary PhD project. Send a CV, a motivation letter, master scores/ranking and reference letters to matteo.rauzi@univ-cotedazur.fr and jocelyn.etienne@univ-grenoble-alpes.fr

/ Job Offers, Open, RAUZI

2017 - HFSP CDA

2017 - ATIP-Avenir

2016 - ANR T-ERC

2012 - HFSP Long Term Fellowship

2011 - Embo-Marie Curie Long Term Fellowship

Popkova et al. from the Rauzi team publish in Dev. Cell a pioneer work on morphogenetic waves during embryonic development.

A morphogenetic wave travels along a biochemical guide to sculpt an epithelial furrow during embryo development Epithelial furrowing is a ...
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MECABIONIC Symposium – Mechanobiology across scales: from the molecule to the organism and back

https://mecabionic.sciencesconf.org/ Contacts: matteo.rauzi@univ.cotedazur.fr rachele.allena@univ.cotedazur.fr ...
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The embryo puts on a string to initiate gastrulation

Embryo gastrulation is the process by which the blastoderm tissue is remodeled and different groups of cells are translocated in ...
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A two-tier junctional mechanism drives composite morphogenesis

Morphogenesis is the process via which tissue shape is remodeled to give form to life during embryo development. Understanding the ...
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The egg puts on a corset to get the right shape

Thanks to an interdisciplinary and exciting collaboration between the iBV and the CBI in Toulouse, the Rauzi and the Wang ...
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UCA annual Award Ceremony: 7 iBV members recognised for their scientific contributions

iBV is a member of Université Cote d’Azur (UCA), a cluster of Research and Higher Education on the French Riviera. Each ...
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iBV - Institut de Biologie Valrose

"Sciences Naturelles"

Université Nice Sophia Antipolis
Faculté des Sciences
Parc Valrose
06108 Nice cedex 2