Since 2009 : Researcher at the Institute of Functional Genomics -IGF-
INSERM U1191, CNRS UMR 5203, Montpellier, France
Role of Imprinted Genes in Cerebral Cortex Development
2006-2009: Post-doc in Pierre Vanderhaeghen's lab
Free University of Brussels, Belgium
Generation of Cerebral Cortex from Embryonic Stem Cells
2002-2006: Post-doc in Jeremy Henley's lab
MRC Centre for Synaptic Plasticty, Bristol, UK
Trafic of the Calcium Sensing Receptor
2002: PhD in Neurosciences
Signaling by the Neurotrophic peptide PACAP
Neurodegenerative diseases, including those affecting the cerebral cortex, are major societal concerns. There is no neurogenesis in the adult cortex to compensate for neuronal loss caused by disease or injury. One emerging solution for cortical diseases is cell therapy, which consists in generating cortical-like neurons in vitro, out of the body, and then grafting these neurons into the nervous system of an host.
When postdoc in Pierre Vanderhaeghen's lab, I was involved in setting up an in vitro corticogenesis system starting from pluripotent mouse embryonic stem cells (ESCs). This system opens new perspectives in the field as we showed that the cellular complexity of the cortex can be faithfully recapitulated in vitro; The system generates cortical-like cells that can be successfully grafted in vivo. Provided we can fully control the proliferation status of neuronal precursors and direct the differentiation process towards the desired phenotype, this system paves the way to the generation of cortical neurons suitable for cerebral cortex cell therapy.
I currently work in Laurent Journot's lab, which is interested in the function of imprinted genes (IGs). IGs are monoallelically expressed and the silenced allele is selected according to its parental origin. Inappropiate levels of IGs cause several brain diseases such as Angelman disease.
We have shown recently that in non-neural systems, IGs, although seemingly functionally disparate, work in the same gene network to control the transition from proliferation to differentiation (Al Adhami et al, Genome Research, 2015).
For the cortex specifically, we found that many IGs are expressed both in the cortex generated in vivo and in the cortex generated in vitro from ESCs. As it is important that cortical neurons generated in vitro resemble as much as possible to the in vivo situation, we then determined to which extent epigenetic mechanisms crucial for cortex development and function, such as parental genomic iparental mprinting, are recapitulated (or not) by in vitro corticogenesis. We found that in vitro corticogenesis from ESCs recapitulates well the imprinting status of the in vivo cortex. This suggests that this subtype of epeigenetic signature is quite well reproduced in vitro. It also suggests that this model could help to define the poorly identified role(s) of parental imprinting on corticogenesis (Bouschet et al, Cerebral cortex, 2016).
Thus, currently, we work on the role of parental imprintring in cerebral cortex development in normal and pathological situations.