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Helgo SCHMIDT
helgo.schmidt@igbmc.fr
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Structural Investigations On Dynein Complexes Involved In Neocortex Development.

Reference : PhD Helgo Schmidt

Publication de l'offre : 26 janvier 2018

The neocortex is the area in the mammalian brain that is associated with motor, cognitive and perceptual abilities. A key step in neocortex formation is the generation of neuronal progenitors in the ventricular zone of the developing embryonic brain. After their generation, these neuronal progenitors travel to the cortical plate to form the neocortex. The neuronal progenitor cells are generated by mitotic cell division of radial glial progenitor cells (RGPC). The RGPC mitotic cell cycle is strictly coordinated with oscillatory movements of their nuclei, a process that has been coined “interkinetic nuclear migration”. The motor protein dynein and associated components form huge complexes with molecular weights in the 3 MDa range to drive nuclear movements during interkinetic nuclear migration. The disruption of these complexes can cause debilitating brain malformations like Lissencephaly (“smooth brain”), which underscores the importance of dynein for proper brain development.

 

In this project, we aim to reconstitute the dynein complexes responsible for RGPC interkinetic nuclear migration and to investigate their structures by state-of-the-art cryo-electron microscopy. The project will greatly benefit from very recently described methods for the recombinant expression and purification of the 1.4 MDa dynein motor, its 1.2 MDa activator dynactin as well as the excellent access to high-end electron microscopes provided by the IGBMC. The outcome of this research will reveal the molecular basis of dynein recruitment to and activation by RGPC nuclei to characterize a crucial step in neocortex development at the most fundamental level.

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