“Role of MECP2 during early development of the primate cerebral cortex“
The thesis defense will take place on Tuesday, December 10th, at 2pm in the SBRI conference room
Jury:
Dr. Colette Dehay (Thesis director)
Dr. Florence Wianny (Co-supervisor)
Pr. Elena Taverna (Reviewer, Human Technopole, University of Milan)
Pr. David Price (Reviewer, Centre for Discovery Brain Sciences, University of Edinburgh)
Pr. Serge Nataf (President of the jury, University Claude Bernard Lyon 1)
During my thesis I have been interested in the role of MECP2 at early stages of cortical development in human and non-human primates. MECP2 (methyl-CpG binding protein 2) is a X-linked gene associated with two main severe neurological disorders, Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), both characterized by a postnatal onset of symptoms. While most functional studies of MECP2 have focused on later stages of cortical development, its role during early development of the cerebral cortex in humans and non-human primates remains largely unknown. In the first part of my thesis, I provided a detailed description of MECP2 expression patterns and timetable in the developing cortex of non-human primates and humans. My findings reported a rostral-caudal gradient of increasing MECP2 expression reminiscent of the rostral-caudal maturation gradient of cortical areas as well as an apical-basal gradient in the developing cortical wall. In the second part, to explore the early role of MECP2, we implemented a targeted overexpression of MECP2 in cortical progenitors generating infragranular (E65) and supragranular layer neurons (E78) in the macaque developing cortex. We report significant consequences on cell-cycle parameters of distinct progenitor types affecting proliferation kinetics, mode of division and cell lineage progression. Additionally, we document the effect of MECP2 overexpression on the dynamics of radial migration and the maturation of newborn neurons.
