Description

How tissues and organs acquire their shape is a central question in biology. Since D’Arcy Thompson’s seminal work On Growth and Form, mechanical forces have been considered key drivers of biological shapes and their diversity across species. Over the past decades, many studies have shown that morphogenesis—the process by which tissues and organs acquire their shape—results from the interplay between molecular signals and mechanical cues, such as forces generated by cells or the rigidity of tissues1,2,3,4. More recently, comparative and theoretical studies have suggested that variations in these mechanical properties may contribute to differences in organ shape between species, alongside classical genetic mechanisms5,6,7,8. Despite this progress, most mechanobiology studies treat tissues as isolated systems, focusing mainly on their internal mechanical properties. However, developing tissues exist in a crowded and dynamic embryonic environment, where they are constantly exposed to forces produced by neighboring tissues9,10,11. The extracellular matrix (ECM), which forms the main component of the interface between tissues, is ideally positioned to transmit these forces. Although recent work suggests that forces transmitted through the ECM can influence organ shape and position12,13, their broader role in morphogenesis—and whether such interactions represent a general developmental strategy that evolution can use to generate organ shape diversity—remains largely unexplored.

To address these questions, we will develop an interdisciplinary approach at the interface of biology (Marie Breau’s group, PhD supervisor) and biophysics (Léa-Laetitia Pontani’s group, PhD co-supervisor). We will study the development of the olfactory placode, a well-defined three-dimensional organ whose formation depends on coordinated cell movements, including a passive expansion of the tissue along the medio-lateral axis14,15,16. Marie Breau’s team has shown that this expansion is not driven by the olfactory placode cells themselves, but instead results from forces generated by adjacent eye development and transmitted to the placode through the interstitial ECM15,16. This system therefore offers a unique opportunity to directly examine how forces originating in one tissue can be transmitted across an interface to shape a neighboring organ. We will combine live imaging of cell and tissue movements with measurements of tissue shape, mechanical forces, and material properties such as stiffness and viscosity. We will begin with zebrafish embryos, which are particularly well suited for live imaging due to their transparency and for targeted perturbations thanks to their genetic accessibility. However, studying a single species is not sufficient to determine whether mechanical interactions between tissues represent a universal developmental principle. We will therefore compare zebrafish with Astyanax mexicanus17,18, a non-model teleost species that naturally displays distinct olfactory placode and eye configurations, to test whether differences in mechanical parameters correlate with differences in organ shape. Finally, we will assess the functional role of the identified mechanical parameters by performing targeted perturbations of the mechanical coupling in zebrafish.

Overall, this PhD project will integrate concepts and methods from developmental biology, biophysics, and evolutionary biology to better understand how mechanical coupling between tissues shapes organs and contributes to their diversification across evolution.

Compétences requises

Student in biology or biophysics interested in tissue morphogenesis

Bibliographie

References:
1. Mammoto T, Ingber DE. doi: 10.1242/dev.024166.
2. Kindberg A, Hu JK, Bush JO. doi: 10.1016/j.ceb.2020.05.004.
3. Heisenberg CP, Bellaïche Y. doi: 10.1016/j.cell.2013.05.008.
4. Espina et al., doi: 10.1242/jcs.260985.
5. Ghosh S et al., doi: 10.1016/j.semcdb.2025.103645.
6. Curantz C et al., doi: 10.1371/journal.pbio.3001807.
7. Bailleul R et al., bioRxiv 2025.02.07.637025
8. Loffet EA, Durel JF, Nerurkar NL. doi: 10.1093/icb/icad033.
9. Villedieu A, Bosveld F, Bellaïche Y. doi: 10.1016/j.gde.2020.03.003.
10. Smith SJ, Guillon E & Holley SA. doi: 10.1242/jcs.259579
11. Elosegui-Artola. doi: 10.1016/j.ceb.2021.04.002
12. Guillon E et al., doi: 10.1073/pnas.1900819116.
13. Tlili S et al., doi: 10.7554/eLife.48964.
14. Aguillon R et al., doi: 10.1242/dev.192971
15. Breau et al., doi: 10.1038/s41467-017-00283-3.
16. Monnot P et al., doi: 10.15252/embr.202152963
17. Hinaux H et al., doi: 10.1242/dev.141291.
18. Devos L et al., doi: 10.1242/bio.059031.

Mots clés

morphogenèse tissulaire, forces mécaniques, poisson-zèbre, imagerie in vivo