Cell and Developmental Biology Seminar Series: Embryonic neural stem cells: From molecular motors to cortical malformations

The neocortex is the centre for higher brain functions, such as perception, decision-making and language. Developmental defects can lead to severe cortical malformations, such as microcephaly or lissencephaly. During normal development, neural stem cells called the apical radial glial (aRG) cells give rise, directly or indirectly, to all neocortical neurons, most glial cells and to the adult stem cells. aRG cells undergo fascinating cell cycle-dependent nuclear oscillations, a process known as Interkinetic Nuclear Migration (INM). I will first present our published results, describing the molecular mechanisms governing INM. I will provide evidence that apical nuclear migration is dependent on the dynein microtubule motor, which is being recruited to the nuclear pore complex during G2 in a Cdk1-dependant manner (Hu*, Baffet* et al., Cell, 2013; Baffet et al., Dev Cell, 2015).
Although the ventricular zone (VZ), where aRG cells are located, is the major neurogenic region in mice, the situation is more complex in humans where the majority of mitoses occur in the outer sub-ventricular zone (OSVZ). As a consequence, this region is massively thicker, which is largely due to a second type of neural stem cells, called the basal Radial Glial (bRG) cells. I will describe ongoing work aimed at developing tools to study these cells, which are believed to be critical to sustain the development of the highly enlarged human brain.