Thèse Cell Motility During Cell Fate Patterning In Caenorhabditis Elegans H/F - 74

Établissement : Ecole normale supérieure - PSL
École doctorale : Complexité du vivant
Laboratoire de recherche : Laboratoire de Physique de l'École normale supérieure
Direction de la thèse : Julie PLASTINO ORCID 0000000278085927
Début de la thèse : 2026-10-01
Date limite de candidature : 2026-06-05T23:59:59

Cells acquire specific fates during development due to the action of diffusible signals called morphogens. Cell position relative to the signaling source is important, and furthermore cells can position themselves within gradients by undergoing actin-based motility, thus changing their exposure.

This interplay between diffusible signals and cell motility is important for the cell positioning that occurs in the developing vulva of the nematode Caenorhabditis elegans. The master organizer of this process is the anchor cell in the uterine epithelial tissue, which secretes a diffusible EGF-like signal to six vulval precursor cells in the ventral epidermis. The precursor cells are born small and distant from each other, with variable positions relative to the anchor cell. They progressively grow until they form a continuous row; those that receive the EGF signal from the anchor cell tend to move towards it, with one of the central vulval precursor cells ending up perfectly aligned under the anchor cell and forming the vulva center. During this alignment process, the vulval precursor cells are confined under a basement membrane and deformed by adjoining epidermal and nerve tissues. The goals of this project are to examine the interplay between diffusible developmental signals, cell motility and nuclear movement in the vulval precursor cells with the objective of uncovering how quasi-invariant and precise cell positioning is achieved despite mechanical challenges of the microenvironment.

To address this question, we will characterize actin dynamics and nuclear deformation in the vulval precursor cells over the course of their movement by live cell imaging, and perturb dynamics by expressing constitutively active and dominant negative forms of actin polymerization and nuclear envelope proteins (Cdc42, Rac GTPase, Arp2/3 complex, nesprin, SUN) and by performing RNAi. We will probe the link between cytoskeleton and signaling by genetically lowering or elevating the dose of EGF. We will also examine the rheological properties of the vulval precursor cells before, during and after positioning using GEMs (Genetically Encoded Multimeric nanoparticles) to test if changes in cytoplasmic stiffness/crowding in the vulval precursor cells help drive cell motility.

Overall the results of this PhD project will shed light on the complex feed-back between signaling, cell movement and nuclear deformation in a complex environment with applications to pathologies such as cancer metastasis that involve aberrant cell movements.

The host lab has expertise in actin cytoskeleton in development from a biophysical perspective, and furthermore, we will work closely with Marie-Anne Félix of IBENS, who is an expert in vulval development in worms. Many of the worm strains needed for the project have already been produced and/or purchased. The lab is equipped with all the necessary material and light microscopes.

In this project, we will assess the interplay between cell movements and signaling pathways in vulval development in C. elegans to discover how these pathways are inter-related to produce precise and reproducible positioning of the primary-fated VPC beneath the anchor cell. We will pay particular attention to the role of the nucleus in VPC positioning since, as the largest and stiffest organelle in the cell, it could hinder correct positioning and active mechanisms may be employed to translocate it.