Morphogenesis, Homeostasis and Pathologies
Galectins are involved in development, immune response and tumorigenesis. Many functions have been ascribed to galectins but evidence is often indirect. We have taken a genetic approach in mice to elucidate the functions and modes of action of galectins 3 and 7.
Galectin 3-/-, galectin 7-/- and double gal3/7 mutant mice are viable and fertile. Characterization of these animal models has now revealed the importance of these proteins in several stress and pathological situations. In the course of these studies, we have established that, in epithelial cells, galectins play a role in cell polarity, intracellular trafficking, and cellular junctions.
While galectin 3 is broadly distributed in the organism, galectin 7 displays a remarkable specificity for stratified epithelia, i.e. namely the epidermis. Our current studies are focused on the maintenance of skin homeostasis following injury, a process that involves both galectin 3 and 7. How do galectins 3 and 7 respectively contribute to epidermal wound healing? This question is addressed using a combination of in vivo approaches with mutant mice and in vitro approaches with keratinocyte cell lines.
Collective cell migration is the main mechanism involved during skin repair after superficial wounding. This movement of keratinocytes depends on the establishment of a new cell polarity and the control of efficient dynamic cell junctions. The coordination of these events is still unclear. Along with unravelling the mode of action of galectins 3 and 7 in the epidermis, this study will also bring a better understanding of collective cell migration, a key phenomenon in tumor progression.
The Institut Jacques Monod animal, imaging, and proteomic plateforms will be instrumental.
Sélection of publications
Gendronneau G, Sanii S, Dang T, Deshayes F, Delacour D, Pichard E, Advedissian T, Sidhu SS, Viguier M, Magnaldo T, Poirier F (2015) Overexpression of galectin-7 in mouse epidermis leads to loss of cell junctions and defective skin repair. PLosOne Mar 5;10(3):e0119031.
Clare DK, Magescas J, Piolot T, Dumoux M, Vesque C, Pichard E, Dang T, Duvauchelle B, Poirier F, Delacour D. (2014) Basal foot MTOC organizes pillar MTs required for coordination of beating cilia. Nat Commun. Sep 12;5:4888.
Comte I, Kim Y, young C, van der Harg JM, Hockberger P, Bolam PL, Poirier F, Szele F (2011) Galectin-3 maintains cell motility from the subventricular zone to the olfactory bulb. J Cell Sci 124: 2438-47.
Koch A, Poirier F, Jacob R, Delacour D. (2010) Galectin-3, a novel centrosome-associated protein, required for epithelial morphogenesis. Mol Biol Cell. 21:219-31.
Gendronneau G, Sidhu SS, Delacour D, Dang T, Calonne C, Houzelstein D, Magnaldo T, Poirier F. (2008) Galectin-7 in the control of epidermal homeostasis after injury. Mol Biol Cell. Dec;19(12):5541-9.