Brain Development and Plasticity

Leader

Research center

45 rue d’Ulm
75230 Paris
Marc Mézard

Institution

Ecole Normale Supérieure
Inserm
CNRS
ED 515 Complexité du Vivant
Université Pierre et Marie Curie

Laboratory

Institut de Biologie de l'ENS IBENS
Phone: 01 44 32 35 47
U1024 - UMR8197
Memolife, PSL

Keywords

Développement cérébral
inflammation prénatale
génétique de la souris
microglies
migration et guidage axonal
Available to host a PhD student

Publications

de Frutos CA, Bouvier G, Arai Y, Thion MS, Lokmane L, Keita M, Garcia-Dominguez M, Charnay P, Hirata T, Riethmacher D, Grove EA, Tissir F, Casado M, Pierani A, Garel S. Reallocation of Olfactory Cajal-Retzius Cells Shapes Neocortex Architecture. Neuron. 2016 Oct 19;92(2):435-448. doi: 10.1016/j.neuron.2016.09.020. 

Lokmane L, Garel S. Map transfer from the thalamus to the neocortex: inputs from the barrel field. Semin Cell Dev Biol. 2014 Nov;35:147-55. doi: 10.1016/j.semcdb.2014.07.005. Epub 2014 Jul 11.


Deck M, Lokmane L, Chauvet S, Mailhes C, Keita M, Niquille M, Yoshida M, Yoshida Y, Lebrand C, Mann F, Grove EA, Garel S. Pathfinding of corticothalamic axons relies on a rendezvous with thalamic projections. Neuron. 2013 Feb 6;77(3):472-84. doi: 10.1016/j.neuron.2012.11.031.

Lopez-Bendito*, G., Cautinat*, A., Sanchez, J.A., Bielle, F., Flames, N., Garrat, A.N., Talmage, D., Role, L.W., Charnay, P., Marin*, O. & Garel*, S. Tangential neuronal migration controls axon guidance : a role for neuregulin-1 in thalamocortical axon navigation. (2006) Cell, 125(1):127-42.

Storm*, E.E., Garel*, S., Borello*, U., Hebert, J.M., Martinez, S., McConnell, S.K., Martin, G.R. & Rubenstein, J.L.R. (2006) Dosage dependent functions of Fgf8 in regulating telencephalic patterning centers. (2006) Development, 133, 1831-44.

Garel, S. & Rubenstein, J.L.R., (2005). Patterning of the cerebral cortex. Cognitive Neuroscience III, (Gazzaniga MS, ed). Cambridge: MA, MIT Press.

Huffman, K.J., Garel, S. & Rubenstein, J.L.R., (2004). Fgf8 regulates the development of intra-neocortical projections. J. Neurosci., 24, 8917-8923.

Garel, S. & Rubenstein, J.L.R., (2004). Intermediate targets in the formation of topographic projections: inputs from the thalamocortical system. Trends Neurosci., 27, 533-39.

Fields of research

Neurogenetics / neurodevelopment

Research Theme

The long-term goal of our laboratory is to understand how the anterior part of the mammalian brain, the telencephalon, is shaped and wired during development. The telencephalon, comprising the cerebral cortex and basal ganglia, plays essential roles such as motor control, sensory perception, and cognitive functions. Its complex neuronal networks are assembled during embryogenesis and remodeled during early postnatal life. During this process, both cell migration and axon guidance play essential roles by controlling the accurate positioning of neuronal subtypes and the formation of specific connections, respectively. Whereas conserved sets of factors have been shown to control cell migration and axon guidance, there is still much to learn about how these two fundamental processes are controlled and coordinated to ensure the morphogenesis of neural circuits in vivo.

By combining mouse molecular genetics, ex-vivo manipulations and advanced imaging techniques, we investigate how cell migration and axon pathfinding are controlled and coordinated to ensure the morphogenesis of neural networks in the developing telencephalon. As developmental abnormalities participate in the etiology of several neuropsychiatric disorders, understanding how the telencephalon wires is essential not only to gain insights into its normal functioning, but also to advance our comprehension of neuropsychiatric disorders. 

ENP Students

Andrea TINTERRI

Team members

ALVAREZ DE FRUTOS Cristina
DECK Marie
KEITA Maryama
LOKMANE Ludmilla
OLLER Guilaume
SQUARZONI Paola

Lab rotation

Axonal plasticity of thalamocortical inputs during early life

Team leader: 

GAREL Sonia

Dates: 

September 1, 2016 - December 31, 2016

Application deadline: 

September 1, 2016

~ Sep-Dec 2016 ~ Jan-March 2017 ~ Apr-June 2017

Project:

 Brain functioning relies on the formation of stereotyped axonal connections. In mammals, the neocortex is organized in different areas receiving specific sensory and motor information via subsets of thalamocortical axons (TCA) topographically organized. Two sequential and independent developmental processes are required for the formation of functional cortical maps: i) extracortical cues initially control TCA pathfinding en route to the neocortex while ii) intrinsic neocortical informations then governs specific matching between TCA and their target areas. Indeed, it is known that modification of cortical regionalization induces a rerouting of TCA in the neocortex and a subsequent displacement of the cortical maps. Conversely, we have shown that aberrant initial TCA pathfinding (Dlx5/6::cre; Ebf1fl/- mutants) leads to an axonal rerouting in the neocortex that recovers innervation with respective cortical targets. How is this remarkable plastic axonal remodelling is controlled and how it impacts on cortical function remain largely to be explored. By taking advantage of the Dlx5/6::cre; Ebf1fl/- mutants, we will characterize the impact of axonal rerouting on cortical regionalization using immunohistochemistry and in situ hybridization. Furthermore, we are currently assessing the factors that regulate and modulate TCA plasticity in this model. Our study thus provides novel mechanistic insights into axonal plasticity and cortical wiring.

Address: Ecole Normale Superieure, Institut de Biologie IBENS, Brain Development and Plasticity, 46, rue d’Ulm 75005 Paris

Phone: 01 44 32 37 25

Email: lokmane@biologie.ens.fr

Website

Supervisor: 

Ludmilla LOKMANE