Cortical development and pathology



Research center

17 rue du Fer à Moulin
75005 Paris


Université Pierre et Marie Curie
Université Pierre et Marie Curie


Marianne Coutures
Phone: 01 45 87 61 35


genetic mouse model
neuropsychiatric disorders
cortical development
epilepsy and intellectual disability
molecular and cellular mechanisms


Bahi-Buisson N, Souville I, Fourniol F, Toussaint A, Moores C, Houdusse A, Lemaitre J-Y, Poirier K, Khalaf-Nazzal R, Hully M, Leger PL, Elie C, Boddaert N, Beldjord C, Chelly, J, Francis, F. (2013) SBH-LIS European consortium  New insights into genotype-phenotype correlations for the DCX-related lissencephaly spectrum. Brain 136:223-244.

Belvindrah R, Natarajan K, Shabajee P, Bruel-Jungerman E, Bernard J, Goutierre M, Moutkine I, Jaglin XH, Savariradjane M, Irinopoulou T, Poncer J-C, Janke C, Francis F. (2017) Mutation of the α-tubulin Tuba1a leads to straighter microtubules and perturbs neuronal migration. J Cell Biol. 216:2443-2461.

*Khalaf-Nazzal R, *Stouffer MA, Olaso R, Muresan L, Roumegous A, Lavilla V, Carpentier W, Moutkine I, Dumont S, Albaud B, Cagnard N, Roest Crollius H, Francis F. (2017) Early born neurons are abnormally positioned in the doublecortin knockout hippocampus. Hum Mol Genet. 26:90-108.

Klingler E, Martin P-M*, Garcia M*, Moreau-Fauvarque C, Falk J, Chareyre K, Giovannini M, Chédotal A, Girault J-A, Goutebroze L. (2015) The cytoskeleton-associated protein SCHIP-1 is involved in axon guidance and required for piriform cortex and anterior commissure development. Development 142:2026-2036.

*Kielar M, *Phan Dinh Tuy F, *Bizzotto S, *Lebrand C, de Juan C, Poirier K, Oegema R, Mancini GM, Bahi-Buisson N, Olaso R, Le Moing AG, Boutourlinsky K, Boucher D, Carpentier W, Berquin P, Deleuze JF, Belvindrah R, Borrell V, Welker E, Chelly J, Croquelois A#, Francis F#. (2014) Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human. Nat Neurosci. 17: 923–933.

Fields of research

Neurogenetics / neurodevelopment

Research Theme

The group of F. Francis/L. Goutebroze focuses on three cortical development proteins mutated in malformations or more subtle cortical abnormalities. Cortical malformations are frequent causes of drug-resistant epilepsy and intellectual disability. More subtle abnormalities may be underestimated in idiopathic and mesial temporal lobe epilepsies and in neuropsychiatric disorders. Cortical defects can arise through abnormal neuronal proliferation, migration and/or connectivity. We use the Eml1, Caspr2 and Dcx proteins as points of entry to better understand normal cortical development and physiopathology. We found that Eml1, likely to be involved in microtubule and membrane dynamics, is mutated in severe subcortical heterotopia, associated with mis-positioned neurons in the white matter. Its role in cortical development is currently unknown. We will study Eml1 in mouse neuronal progenitors and post-mitotic neurons and question potentially novel mechanisms leading to heterotopia. Mutations in Caspr2, an adhesion protein, are found in a wide spectrum of disorders, including syndromic epilepsy and autism. Better known for its roles at the nodes of Ranvier, its neurodevelopmental functions have been little-studied. It may be essential for adhesive capacities of migrating neurons and during the formation of synapses at the axonal initial segment, which we will test here. We will also question the consequences of patient mutations on these functions. DCX, a microtubule-associated protein is mutated in heterotopia and severe gyral abnormalities. Dcx knockout mice are an excellent model to study aberrant connectivity and hyperexcitability related to migration defects, epilepsy and behavioral abnormalities. Studying mutant mice and patient mutations for these three proteins will reveal novel insights into the causes and consequences of abnormal neuronal positioning and connectivity, related to cortical malformations and neuropsychiatric disorders.

ENP Students