Our group is interested in the molecular and cellular mechanisms underlying morphogenesis of the vertebrate brain, and in the perturbations of these processes in human diseases affecting brain development. We are more particularly interested in studying cell polarity processes and the dynamic localisation of intracellular cues and the function of organelles such as cilia.

• The main project of the group aims at dissecting the functions of the primary cilium in brain morphogenesis using the mouse and zebrafish as model systems. Primary cilia are microtubular organelles with sensory functions, whose defects lead to human diseases called ciliopathies. We mainly focus on the Ftm/Rpgrip1l gene, which codes for a ciliary protein and is involved in severe ciliopathies with associated brain abnormalities. We investigate the function of this gene in brain morphogenesis, cell behaviour and signalling pathways.

We studied the function of Rpgrip1l in mice and zebrafish. We have shown that this protein plays a role in the regionalization of the telencephalon and the morphogenesis of the olfactory bulb and the corpus callosum in mice, via the formation of a repressor form of the transcription factor Gli3. These data explain the appearance of agenesis of these structures in ciliopathies (Besse et al., 2011; Laclef et al., 2015; Andreu-Cervera et al., 2019). We also identified an original role for Rpgrip1l in the establishment of planar polarity (PCP). Loss of function of Rpgrip1l leads to PCP defects in the murine cochlea and the floor of the neural tube in fish. We have shown that Rpgrip1l controls this process in part by stabilizing the Dishevelled protein (Mahuzier et al., 2012).

Nous poursuivrons notre étude des fonctions diverses des cils primaires dans la morphogenèse du cerveau antérieur et dans la polarité planaire, en exploitant les modèles souris et poisson zèbre, et des outils multiples disponibles au laboratoire. Nous voulons en particulier aborder la dynamique de l’établissement de la PCP dans la plaque du plancher du poisson zèbre en utilisant l’imagerie sur embryons vivants.

- Ruxandra Bachmann & Stephan Neuhauss, University of Zürich, Switzerland.  

- Bénédicte Durand, Université de Lyon, France.

- Christoph Gerhardt & Uli Rüther, Heinrich Heine University, Düsseldorf, Germany. 

- Cecilia Moens, Fred Hutchinson Cancer Research Center, Seattle, USA. 

- Mireille Montcouquiol, Institut Magendie, Bordeaux, France

- Sophie Saunier, Institut Imagine, Hopital Necker, Paris, France. 

- Thomas Theil, University of Edinburgh, UK