About Dr. Mireille Montcouquiol

Our team "Planar Polarity and Plasticity" aims at understanding how Planar Cell Polarity (PCP) signaling shapes the brain, with a broad interest extending from molecular complexes to higher brain function and diseases.

PCP was originally identified in invertebrate's epithelia, which is why most studies pertain to this tissue. Ten years ago, two pioneering studies – including our work in Nature - led to the identification of two of the first of these PCP genes in mammals, Vangl2 and Scrib1, (Montcouquiol et al., 2003), and Celrs1 (Curtin et al., 2003). Those studies in the inner ear were the starting point to an explosion of studies relating the importance of PCP signaling in many tissues including muscles, heart, vessels, bones, or the nervous system, and related pathologies (neural tube defects, polycystic kidney disease, cardiac, muscles, vessels or bones malformation). Unfortunately, all mice with spontaneous PCP gene mutations display craniorachischisis, the most severe form of neural tube defect, leading to neonatal lethality and the destruction of brain structure. Human mutations of PCP genes have also been directly linked to neural tube defects, which is one of the most common birth defects occurring in approximately one in 1,000 births (Copp et al., 2013). Recent studies have identified mutations on PCP proteins in autistic patients (Scrib1: Neale et al, 2012; Pinto et al, 2010, Prickle2: Sowers et al., 2013), or other pathologies like epilepsy or ataxia (Fox and Bassuk, 2009; Tao et al., 2011). Although scarce, data on PCP signaling disruption in mice have revealed sociability defects and memory imbalance, typical of ASD (Long 2004; Moreau et al., 2010; Sowers et al., 2013). To the already long list of pathologies associated with PCP signaling defects, recent studies have emphasize a link between PCP and ciliopathies (Wallingford, 2010), a link that we partially elucidated recently (Ezan et al., 2013). All these PCP-related pathologies represent a considerable social and economic burden in France and in the world. Thus, investing in the understanding of the basic mechanism of PCP at the base of these pathologies would bring enormous economic and social returns.

Our project relies on specific genetic tools and strong PCP expertise. We have a double expertise in the inner ear -the bona fide model system to study PCP in mammals-, and in the brain, that give us an original and unique perspective to address the role of PCP signaling in the nervous.

Key words: polarity, autism, ASD, epilepsy, centrosome, cilia, tubulin, actin, cytoskeleton, cortex, hippocampus, cochlea, hair cell, neurons

For more information, please also see http://www.neurocentre-magendie.fr/NCM_Pages/Equipes/eq_montcouquiol-sans/UK_equipe_montcouquiol-sans.php

A full publication record can be found here.