Annonce en anglais

Project title: Pattern formation by self-organized cell movement.

Type of rotation: M2 (6 months)

Supervisors: Virginie Thomé and Laurent Kodjabachian

Concept and Objectives

Vertebrate animals possess specialized epithelia containing multiciliated cells (MCCs), whose hundreds of motile cilia beat coordinately to generate directional fluid flow (1). In humans, MCCs help airway cleansing, ovum implantation and cerebrospinal fluid circulation. Understanding the biology of MCCs is a fundamental issue with high biomedical relevance, as their dysfunction can cause severe respiratory syndromes and infertility.

Our team studies MCCs in three experimental paradigms: the multiciliated skin of the amphibian Xenopus laevis embryo, which is well suited for simple and efficient functional analysis (2); the mouse post-natal brain, which is amenable to super-resolution microscopy (3); a newly developed model of in vitro MCC culture, particularly well adapted to proteomics (unpublished).

Recently, we have uncovered some of the principles underlying regular MCC spatial distribution in the Xenopus epidermis (4,5), which involves mutual repulsion mediated by a ligand/receptor couple. Furthermore, we have obtained evidence that regular MCC spatial distribution is essential to clear the surface of the embryo from incoming pathogens. For this project, it is proposed to further study the molecular control of MCC patterning.

The selected candidate will receive training in the following areas: molecular biology, cell biology, Xenopus micro-injection and micro-surgery, fluorescent confocal microscopy, video-microscopy, numerical image analysis. Command of English is compulsory. The selected candidate must have received a solid background in one or more of the following subjects: cell biology, developmental biology, molecular biology.

References

• Boutin, C. and Kodjabachian, L. 2019. Biology of multiciliated cells. Opin. Genet. Dev. 56, 1-7.
• Marcet, B., Chevalier, B^¶., Luxardi, G^¶., Coraux, C^¶., Zaragosi, E., Cibois, M., Robbe-Sermesant, K., Jolly, T., Cardinaud, B., Moreilhon, C., Giovannini-Chami, L., Nawrocki-Raby, B., Birembaut, P., Waldmann, R., Kodjabachian, L*. and Barbry, P*. 2011. Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway. Cell Biol. 13, 694-701.
• Revinski, DR^†., Zaragosi, L-E^†., Boutin, C^†., Ruiz Garcia, S., Deprez, M., Rosnet, O., Thomé, V., Mercey, O., Paquet, A., Pons, N., Marcet, B^*., Kodjabachian, L^*. and Barbry, P^*. 2018. CDC20B is required for deuterosome-mediated centriole production in multiciliated cells. equal contribution^†, corresponding authors^*. Nature Communications. 9:4668.
• Chuyen, A., Rulquin, C., Daian, F., Thome, V., Clement, R., Kodjabachian, L*. and Pasini, A*. 2021. The Scf/Kit pathway implements self-organized epithelial patterning. Developmental Cell. 56:795-810. Preview by Michel Milinkovitch: Emergence of self-organizational patterning at the mesoscopic scale. Developmental Cell. 56:719-721. Alexandre Chuyen awarded 2020 SFBD Best Thesis Prize.
• Chuyen, A., Daian, F., Pasini, A. and Kodjabachian, L. 2021. Analysis of multiciliated cell movement in Xenopus laevis embryos, from live imaging to data processing. STAR Protocols. 2(4):100928.