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Conference by Adrien Meguerditchian

Published on March 28, 2017

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Stem cells and cortical development


The central focus of our work is aimed at deciphering the relative contribution of the multiple factors that specify neocortical areas, with an emphasis on the role of cell-cycle modulation of cortical neuroblasts.

Generation of rhesus ES cell-derived astrocytes engineered to support maturation and survival of mesencephalic dopaminergic neurons.
Embryonic stem (ES) cells are thought to offer the most promise for yielding dopaminergic (DA) neurons suitable for transplantation in Parkinson’s disease. However, in all the transplantation studies based on TH+ neurons produced from ES cells the degree of DA cell survival following transplantation is small and the magnitude of behavioral benefit is modest. These results are thus encouraging, but underline the need for improved methods to promote the maintainance of differentiation and the survival of dopamine neuron after transplantation in order to expect to attain long-lasting benefits in Parkinsonian’s disease patients. To overcome this limitation, we shall develop a strategy based on the generation of astrocytes genetically engineered so as to express and release factors promoting differentiation and survival of midbrain dopamine neurons. Making use of the LYON-ES cell-line that we have isolated (Wianny et al., 2008) we shall generate astrocytes producing Wnt5a and/or GDNF. These engineered astrocytes will then be transplanted into the striatum of MPTP-treated monkeys together with DA neurons in collaboration with E. Procyk and P. Savatier teams.

Colette Dehay

Team leader

Angèle Bellemin-Ménard

Ugo Borello

Veronique Cortay

I am a research assistant engineer. My interest concerns the study of cortical development. I analyse proliferation, differentiation and migration in the developing cortex using cell biology techniques. I routinely perform immunohistochemistry, dissociated cell culture, organotypic culture of embryonic brain and time-lapse videomicroscopy. Recently I have focused my efforts on 2 photons imaging of GFP/RFP expressing precursors on organotypic slices.

Besides performing ...

Delphine Delaunay

The cerebral cortex is constituted by different type of neuronal cells working together to sustain most of our cognitive abilities. One critical step that ensures this higher function is the birth of the proper type and number of neurons during development. My project will contribute to this issue by examining the mode of cell division in the mouse Neocortex during development with a special emphasis on the Wnt/planar cell polarity pathway and its function in promoting ...

Nathalie Doerflinger

Molecular biology : cloning, PCR and qPCR (on DNA, RT or single cell cytoplasm), LCM, RNA microarray, RNAi (siRNA and shRNA), ISH, IHC,...

Julie Fousse

Cyril Huissoud

Dorothee Lamy

Cortical development, Cell cycle, Cell proliferation.

Claire Millet

Clarisse Pace

Nolwenn Pasquet

Cloe Rognard

Florence Wianny

My research interests include neural stem cells derived from Embryonic Stem cells in the non-human primate, the study of their self-renewal, and their differential potential.

Heather Wild

I completed my PhD in the structure and function of the mammalian visual system in 1984 in the UK and  then coordinated research studies with stroke patients. Since being in Lyon, I have returned to basic neuroscience involving neuroimagery of the human brain. I am currently involved with Ugo Borello and Colette DeHay in discovering patterns of gene expression during development.

Selected Publications of Team members :
Pfeiffer M, Betizeau M, Waltispurger J, Pfister SS, Douglas RJ, Kennedy H, Dehay C (2016) Unsupervised lineage-based characterization of primate precursors reveals high proliferative and morphological diversity in the OSVZ. J Comp Neurol. 2016; 524:535-63
Fame RM, Dehay C, Kennedy H, Macklis JD (2016) Subtype-specific genes that characterize subpopulations of callosal projection neurons in mouse identify molecularly homologous populations in macaque cortex. Cereb Cortex, in press 10.1093/cercor/bhw023
Delaunay D, Robini MC, Dehay C (2015) Mitotic spindle asymmetry in rodents and primates: 2D vs. 3D measurement methodologies Front Cell Neurosci. 2015 Feb 9;9:33
Adnani L, Langevin LM, Gautier E, Dixit R, Parsons K, Li S, Kaushik G, Wilkinson G, Wilson R, Childs S, Nguyen MD, Journot L, Dehay C, Schuurmans C. (2015) Zac1 regulates the differentiation and migration of neocortical neurons via Pac1 J Neurosci. 2015 Sep 30;35(39):13430-47. doi: 10.1523/JNEUROSCI.0777-15.2015.
Dehay C, Kennedy H, Kosik KS (2015) The outer subventricular zone and primate-specific cortical complexification. Neuron, 85:693-94
Pilaz LJ, Patti D, Marcy G, Ollier E, Pfister S, Douglas RJ, Betizeau M, Gautier E, Cortay V, Doerflinger N, Kennedy H, Dehay C (2009) Forced G1-phase reduction alters mode of division, neuron number, and laminar phenotype in the cerebral cortex. Proc Natl Acad Sci USA, 2009, 106:21924-21929 download
Wianny F, Bernat A, Huissoud C, Marcy G, Markossian S, Cortay V, Giroud P, Leviel V, Kennedy H, Savatier P, Dehay C (2008) Derivation and cloning of a Novel Rhesus ES cell line stably expressing Tau-GFP. Stem Cells. 2008 26(6):1444-1453 download
Fish JL, Dehay C, Kennedy H, Huttner WB (2008) Making bigger brains-the evolution of neural-progenitor-cell division. J Cell Sci. 2008 121(Pt 17):2783-93 download
Dehay C, Kennedy H (2007) Cell-cycle control and cortical development. Nat Rev Neurosci, 2007, 8(6):438-50 download
Fluckiger AC, Marcy G, Marchand M, Negre D, Cosset FL, Mitalipov S, Wolf D, Savatier P, Dehay C (2006) Cell cycle features of Primate Embryonic Stem Cells Stem Cells 24(3):547-556 download
Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M Jr, Vanderhaegen P & Haussler D (2006) An RNA gene expressed during cortical development evolved rapidly in humans Nature 443:167-72 download
Lukaszewicz A, Cortay V, Giroud P, Berland M, Smart I, Kennedy H, Dehay C (2006) The concerted modulation of proliferation and migration contributes to the specification of the cytoarchitecture and dimensions of cortical areas. Cereb Cortex, 2006, 16 Suppl 1:i26-34 download
Lukaszewicz A, Savatier P, Cortay V, Giroud P, Huissoud C, Berland M, Kennedy H, Dehay C (2005) G1 phase regulation, Area-Specific cell cycle control, and Cytoarchitectonics in the Primate Cortex. Neuron, 2005, 47:353-364 download
Lukaszewicz A, Savatier P, Cortay V, Kennedy H, Dehay C (2002) Contrasting Effects of Basic Fibroblast Growth Factor and Neurotrophin 3 on Cell Cycle Kinetics of Mouse Cortical Stem Cells. J Neurosci, 2002, 12(5) : 6610-6622 download
Smart IH, Dehay C, Giroud P, Berland M, Kennedy H (2002) Unique Morphological Features of the Proliferative Zones and Postmitotic Compartments of the Neural Epithelium Giving Rise to Striate and Extrastriate Cortex in the Monkey Cerebral Cortex 12:37-53 download
Dehay C, Savatier P, Cortay V, Kennedy H (2001) Cell-cycle kinetics of neocortical precursors are influenced by embryonic thalamic axons. J Neurosci, 2001, 21:201-214 download