Morphogenesis, Homeostasis and Pathologies

Galectins are multifunctional proteins which are involved in development, immune response and tumorigenesis. These proteins have been implicated in cell interactions, cell cycle, apoptosis and intracellular trafficking but evidence is often indirect.  

The goal of the team is to elucidate the function and mechanisms of action of galectins using the different mutant mouse lines that we have generated.

Null mutant mice, either galectin 1-/-, galectin 3-/- or galectin 7-/-, are all viable and fertile. Characterization of these animal models has revealed the importance of these proteins in various stress or pathological situations. Thus, galectin 1 plays a role in the myogenic lineage (figure 1), notably in muscle repair after injury, galectin 3 in epithelial morphogenesis (intracellular trafficking and polarity) (figure 2) and galectin 7 in epidermal regeneration during wound healing (figure 3).

Figure 1: Distribution of galectin 1 transcripts in a 9.75 day old mouse embryo. Galectin 1 expression is intense in the somites where the myogenic precursors are located.

Figure 2: Immunodetection of a brush border marker, villin (green), in enterocytes of wild type (wt; left) and galectin-3 mutant (gal3-/-; right) mice. Whereas the staining is restricted to the apical surface of wt cells, this polarized distribution is severely perturbed in the absence of galectin-3.

Figure 3: Immunodetection of galectin-7 (green), and β-tubulin (red, left) or cortactin (red, right) at the extremity of cell protrusions in migrating keratinocytes. Colocalization of these proteins indicates that galectin-7 is present inside podosomes.

How are these different functions mediated by galectins' Our current objective is to dissect these mechanisms using appropriate cell culture systems. Modern cell imagery approaches, proteomics and genomics will be carried out with the assistance of the Institut Jacques Monod cores facilities.

These projects are financed by the CNRS, ARC, la Ligue contre le cancer and GEFLUC.

Selection of Publications

Genetic assessment of the importance of galectin-3 in cancer initiation, progression, and dissemination in mice.
Eude-Le Parco I, Gendronneau G, Dang T, Delacour D, Thijssen VL, Edelmann W, Peuchmaur M, Poirier F.
Glycobiology. 2009 Jan;19(1):68-75. Epub 2008 Oct 10.
Abstract

Galectin-7 in the control of epidermal homeostasis after injury.
Gendronneau G, Sidhu SS, Delacour D, Dang T, Calonne C, Houzelstein D, Magnaldo T, Poirier F.
Mol Biol Cell. 2008 Dec;19(12):5541-9. Epub 2008 Oct 1.
Abstract


Loss of galectin-3 impairs membrane polarisation of mouse enterocytes in vivo.
Delacour D, Koch A, Ackermann W, Eude-Le Parco I, Elsässer HP, Poirier F, Jacob R.
J Cell Sci. 2008 Feb 15;121(Pt 4):458-65. Epub 2008 Jan 22.
Abstract


Lack of galectin-1 results in defects in myoblast fusion and muscle regeneration.
Georgiadis V, Stewart HJ, Pollard HJ, Tavsanoglu Y, Prasad R, Horwood J, Deltour L, Goldring K, Poirier F, Lawrence-Watt DJ.
Dev Dyn. 2007 Apr;236(4):1014-24.
Abstract


Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy.
Thijssen VL, Postel R, Brandwijk RJ, Dings RP, Nesmelova I, Satijn S, Verhofstad N, Nakabeppu Y, Baum LG, Bakkers J, Mayo KH, Poirier F, Griffioen AW.
Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):15975-80. Epub 2006 Oct 16.
Abstract

Last modified 03/14/2011

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