Genetics and Development of the Cerebral Cortex

Group leader

Migrating transient neurons and their signaling function during development and evolution of the mammalian cerebral cortex

Our team focuses on the development and evolution of the cerebral cortex. We study how life and death of transient migrating neuronal populations orchestrate the construction of functional cortical circuits during embryogenesis and how dysfunction of developmental processes coordinated by these neurons leads to pathological conditions.

The neocortex is divided into distinct functional areas, which control sensory perception, motor behaviours and cognitive functions. These functions rely on a complex architecture of neural networks that begins to be established during embryonic development. This early developmental phase constitutes a major step in the functional emergence of brain circuits. Indeed, studies spanning the past decades revealed that abnormal brain development participates in the aetiology of several neurological and psychiatric disorders including epilepsy, schizophrenia, autism, spectrum disorders or obsessive-compulsive behaviours. Understanding the fundamental mechanisms governing brain development is thus essential not only to progress our comprehension of the formation of one of the most complex structures but also to provide basic knowledge that will foster future clinical research.

Our team identified the existence of subtypes of Cajal-Retzius cells (CRs) and of unexpected populations of glutamatergic migrating transient neurons (Cortical Plate Transient neurons) derived from Dbx1-expressing progenitors. Through genetic tracing and ablation we showed that Dbx1-derived cells display unique features, as they: a) migrate over very long distances, b) are transient during development and undergo cell death at early postnatal stages, c) signal to neighbouring cells. These transient migrating cells serve as organizers of cortical patterning, fine-tuning of glutamatergic neuronal numbers and survival of craniofacial structures (Griveau, 2010; Teissier, 2010, 2012; Barber, 2015; Causeret, 2011, 2015). We recently showed that the specific distribution of CRs by strictly controlling their migration parameters plays a crucial role in determining the size and wiring of higher-order areas, whose expansion characterizes the primate neocortex (Barber, 2015). Together, our results show that the presence and disappearance of Dbx1-derived transient neurons at a precise time is crucial for the formation of functional cortical circuits.

Our projects are funded by the Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Idex Université Sorbonne Paris Cité, Mairie de Paris, Association pour la Recherche sur le Cancer (ARC), Fédération pour la Recherche sur le Cerveau (FRC),  La Ligue contre le cancer, Neuropôle de recherche francilien (NeRF). The Team is member of the École des Neurosciences de Paris Ile-de-France (ENP).

Selection of publications

Ledonne F., Orduz D., Mercier J., Vigier L., Grove E.A., Tissir F., Angulo M.C., Pierani A. and Coppola. E. Targeted inactivation of Bax reveals subtype-specific mechanism of Cajal-Retzius neuron death in the postnatal cerebral cortex.  Cell Reports (2016), 17, 3133–3141.
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Freret-Hodara B., Cui Y., Griveau A., Vigier L., Arai Y., Touboul J. and Pierani A. Enhanced abventricular proliferation compensates cell death in the embryonic cerebral cortex. Cerebral Cortex (2016) Sept 12;
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Karaz S.#, Courgeon M. #, Lepetit H., Bruno E., Pannone R., Tarallo A., Thouzé F., Kerner P., Vervoort M., Causeret F., Pierani A. and D'Onofrio G. Neuronal fate specification by the Dbx1 transcription factor is linked to the evolutionary acquisition of a novel functional domain. Evodevo (2016) Aug 12; eCollection 2016.
Abstract

Barber, M., Arai, Y., Morishita, Y., Vigier, L., Causeret, F., Borello, U., Ledonne, F., Coppola, E., Contremoulins, V., Pfrieger, F.W., Tissir, F., Govindan, S., Jabaudon, D., Proux-Gillardeaux, V., Galli, T. and Pierani, A. Migration speed of Cajal-Retzius cells modulated by vesicular trafficking controls the size of higher-order cortical areas. Current Biol. (2015), 25, 2466-2478. Epub 2015 Sep 17.
Research Highlight in Nature Reviews Neuroscience (2015), 16, 644-645
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Causeret, F., Sumia, I. and Pierani A. Kremen1 and Dickkopf1 control cell survival in a Wnt-independent manner. Cell Death and Differentiation (2015), Jul 24.
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Teissier A., Waclaw R.R., Griveau A., Campbell K. and Pierani A. Tangentially migrating transient glutamatergic neurons control neurogenesis and maintenance of cerebral cortical progenitor pools. Cerebral Cortex (2012), 22, 403-416. Epub 2011 Jun 10.
Abstract