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.
|2016||524(3):535-63||Unsupervised lineage-based characterization of primate precursors reveals high proliferative and morphological diversity in the OSVZ||Pfeiffer M, Betizeau M, Waltispurger J, Pfister SS, Douglas RJ, Kennedy H, Dehay C||J Comp Neurol||-|
|2015||09:33||Mitotic spindle asymmetry in rodents and primates: 2D vs. 3D measurement methodologies||Delaunay D, Robini MC, Dehay C||Front Cell Neurosci||-|
|2015||85(4):683-94||The outer subventricular zone and primate-specific cortical complexification||Dehay C, Kennedy H, Kosik KS||Neuron||-|
|2014||6(2):400-14||Mitotic spindle asymmetry: a Wnt/PCP-regulated mechanism generating asymmetrical division in cortical precursors||Delaunay D, Cortay V, Patti D, Knoblauch K, Dehay C||Cell Rep||-|
|2014||81(6):1255-62||Novel primate miRNAs coevolved with ancient target genes in germinal zone-specific expression patterns||Arcila ML, Betizeau M, Cambronne XA, Guzman E, Doerflinger N, Bouhallier F, Zhou H, Wu B, Rani N, Bassett DS, Borello U, Huissoud C, Goodman RH, Dehay C, Kosik KS||Neuron||-|