Genetics of mouse brain development

The aims of our work are to elucidate the key mechanisms of neurogenesis in the developing and post-natal cerebral cortex. During corticogenesis, the remarkable array of different neuronal cell types is generated from a complex population of multipotent stem and progenitor cells following a precise spatial and temporal pattern before being assemble in maps and circuits. We are interested in understanding the cellular and molecular mechanisms by which these different neuronal cell types are temporally and spatially regulated by the action of defined regionalized and coordinated differentiation programs.

The mammalian cerebral cortex, which is responsible for high-level perceptual analysis and executive functions, is subdivided into a number of functionally individual areas that process distinct sensory modalities and motor outputs. Cortical areas are defined by their pattern of gene expression, cytoarchitecture, and input/output connectivity. Each area is then radially sub-divided into distinct six layers, and each layer consists of neurons with distinctive functions, morphologies, connectivity pattern and a repertoire of transcription factors expressed in different combinations. Since areas are made of layers and layers build up areas, areal and laminar specification become two closely interrelated processes during corticogenesis.

Areal and laminar identity are initially specified in cortical progenitors by a series of regionalised factors, and then implemented through subsequent processes of fate acquisition by other factors expressed in post-mitotic neurons. Our work has demonstrated a major role of the nuclear receptor COUP-TFI in coordinately regulating areal and laminar identity in a temporally-controlled manner in the mouse developing cerebral cortex.

We have showed that during corticogenesis, COUP-TFI is required in balancing the neocortex into frontal/motor and sensory areas ( Armentano et al., Nature Neuroscience, 2007 ), in controlling the generation of corticospinal motor neurons ( Tomassy et al., PNAS, 2010 ), in axonal outgrowth ( Armentano et al., Development, 2006 ) and in neuronal migration ( Alfano et al., Development, 2011 ).

Schematics on the role for COUP-TFI in controlling the balance between motor and sensory aresa. Areas have distinct cytoarchitecture and connectivity. Motor areas have a thick layer V, whereas sensory areas have a thick layer IV. By controlling area patterning COUP-TFI regulates not only layer and cell-type specification, but also cell migration and axonal elongation.

We plan in the next few years to gain more insights into how cortical realization is linked to the mode of progenitor/stem cell division, fate commitment of mitotic and post-mitotic neurons, activity-dependent mechanisms of cortical cells and thalamocortical topography.

We combine several molecular and cellular approaches, including mouse genetics, developmental neuroanatomy, in utero elctroporation, in vitro and biochemical assays, and neural stem cell cultures.


GFP-expressing cells (green) electoporated at embryonic day 14.5 have migrated to upper layers in a post-natal day 8 mouse neocortex. Red neurons label subcerebral projection neurons in lower layers .

P8 brains electroporated with a GFP-expressing construct at E14.5. GFP labels migrating neurons and projecting axons, in this case callosal projection neurons, innervating the contralateral side.


Last publications

The caudo-ventral pallium is a novel pallial domain expressing Gdf10 and generating Ebf3-positive neurons of the medial amygdala. - 2018 - Brain structure & function - Ruiz-Reig N, Andres B, Lamonerie T, Theil T, Fairén A, and Studer,M

The pleiotropic transcriptional regulator COUP-TFI plays multiple roles in neural development and disease. - 2018 - Brain research - Bertacchi M, Parisot J, and Studer,M

Developmental genetic programs and activity-dependent mechanisms instruct neocortical area mapping. - 2018 - Current opinion in neurobiology - 53 P96-102 - Simi A, and Studer,M

Neuron-Astroglia Cell Fate Decision in the Adult Mouse Hippocampal Neurogenic Niche Is Cell-Intrinsically Controlled by COUP-TFI In Vivo. - 2018 - Cell reports - 24 P329-341 - Bonzano S, Crisci I, Podlesny-Drabiniok A, Rolando C, Krezel W, Studer M, and De Marchis,S

Rostro-Caudal and Caudo-Rostral Migrations in the Telencephalon: Going Forward or Backward? - 2017 - Frontiers in neuroscience - 11 P692 - Ruiz-Reig N, and Studer,M

COUP-TFI mitotically regulates production and migration of dentate granule cells and modulates hippocampal Cxcr4 expression. - 2017 - Development (Cambridge, England) - 144 P2045-2058 - Parisot J, Flore G, Bertacchi M, and Studer,M

Molecular control of two novel migratory paths for CGE-derived interneurons in the developing mouse brain. - 2016 - Development (Cambridge, England) - Touzot A, Ruiz-Reig N, Vitalis T, and Studer,M

Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications. - 2016 - eLife - 5 - Harb K, Magrinelli E, Nicolas CS, Lukianets N, Frangeul L, Pietri M, Sun T, Sandoz G, Grammont F, Jabaudon D, Studer M, and Alfano,C

Gradient COUP-TFI Expression Is Required for Functional Organization of the Hippocampal Septo-Temporal Longitudinal Axis. - 2016 - Cerebral cortex (New York, N.Y. : 1991) - Flore G, Di Ruberto G, Parisot J, Sannino S, Russo F, Illingworth EA, Studer M, and De Leonibus,E

Postmitotic control of sensory area specification during neocortical development. - 2014 - Nature communications - 5 P5632 - Alfano C, Magrinelli E, Harb K, Hevner RF, and Studer,M

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Studer Michele
Group Leader

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Members Team
   Deschaux Olivier
   Di Bonito Maria
   Simi Alessandro
   Felske Torsten
   Serra Linda
   Tocco Chiara
Engineers & Technicians
   Setti Touzri Eya
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    October 2015 - M. Studer Team
   1 POST-DOC position 3 year   Closed

    October 2013 - Michèle Studer Team
   CDD 1 an Assistant ingenieur   Closed



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