Team Pierani

Genetics and Development of the Cerebral Cortex

Resume
Detailed information

Cortical development during early embryonic stages depends on the action of different cell types that are transiently present in the cortex. Both variation in number and diversity of these transient signaling neurons might represent an evolutionary addition to increase brain complexity and cognitive function.

We reported that variations in their migration or their programed cell death disrupt neural circuits. These neurons express at high levels genes whose mutations have been associated with neurological and psychiatric disorders.

By coupling studies on the function of transient neuron development in mice and primates, our future projects aim at linking developmental neuroscience with evolution and pathology in humans.

In particular, they aim at i) molecularly dissecting how these neurons serve as organizers in neocortical development, ii) determining how their acquisition in mammals has contributed to the evolution of the neocortex and iii) testing how their dysfunction affects neural circuits in mouse models and may lead to pathological conditions.

Our projects span from early onset cortical malformations to susceptibility to susceptibility to later-onset diseases characteristic of psychiatric illnesses and this

translational project is developed in collaboration with neuroscientists, human geneticists and clinicians.

Cell identities and migration routes in the developing mouse cortex as revealed by immunohistochemistry

Main Publications

Moreau MX, Saillour Y, Elorriaga V, Bouloudi B, Delberghe E, Deutsch Guerrero T, Ochandorena-Saa A, Maeso-Alonso L, Marques MM, Marin MC, Spassky N, Pierani A, Causeret F. Repurposing of the multiciliation gene regulatory network in fate specification of Cajal-Retzius neurons. Dev Cell. 2023 Aug 7;58(15):1365-1382.e6. doi: 10.1016/j.devcel.2023.05.011. Epub 2023 Jun 14.

Ramezanidoraki N, Ouardi DE, Le M, Moriceau S, Ahmadi M, Elena D, Rolland D, Bun P, Le Pen G, Canaud G, Bahi-Buisson N, Rouach N, Piskorowski R, Pierani A, Billuart P. Activation of the PI3K/AKT/mTOR Pathway in Cajal-Retzius Cells Leads to Their Survival and Increases Susceptibility to Kainate-Induced Seizures. Int J Mol Sci. 2023 Mar 11;24(6). doi: 10.3390/ijms24065376.

Riva M, Moriceau S, Morabito A, Dossi E, Sanchez-Bellot C, Azzam P, Navas-Olive A, Gal B, Dori F, Cid E, Ledonne F, David S, Trovero F, Bartolomucci M, Coppola E, Rebola N, Depaulis A, Rouach N, de la Prida LM, Oury F, Pierani A. Aberrant survival of hippocampal Cajal-Retzius cells leads to memory deficits, gamma rhythmopathies and susceptibility to seizures in adult mice. Nat Commun. 2023 Mar 18;14(1):1531. doi: 10.1038/s41467-023-37249-7

Moreau M, Saillour Y, Cwetsch A, Pierani A, Causeret F. Single-cell transcriptomics of the early developing mouse cerebral cortex disentangles the spatial and temporal components of neuronal fate acquisition. Development. 2021 Jul 15;148(14):dev197962. doi: 10.1242/dev.197962. Epub 2021 Jul 16.

Arai Y, Cwetsch AW, Coppola E, Cipriani S, Nishihara H, Kanki H, Saillour Y, Freret-Hodara B, Dutriaux A, Okada N, Okano H, Dehay C, Nardelli J, Gressens P, Shimogori T, D'Onofrio G, Pierani A. Evolutionary Gain of Dbx1 Expression Drives Subplate Identity in the Cerebral Cortex. Cell Rep. 2019 Oct 15;29(3):645-658.e5. doi: 10.1016/j.celrep.2019.09.007.

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Main techniques/approaches:

We employ a multidisciplinary approach including mouse genetics (cell tracing and ablation, gene knock-out), pharmacological and genetic manipulation during embryogenesis using in vitro and in utero paradigms including electroporation, together with transcriptome profiling, phenotyping using behavioural tests and migration studies using single-cell resolution and time-lapse microscopy.

Furthermore, in collaboration, we also use electrophysiology, optogenetics and mathematical modelling.