Synaptic proteins guide cortical migration and influence cortex folding

A fundamental question in neuroscience is which mechanisms drive folding of the cerebral cortex. One of the most obvious feature of mammalian brain evolution is the expansion of the cortex, which is generally accompanied by substantial folding of the cortical surface into valleys (gyri) and ridges (sulci). This process represents a fascinating evolutionary step that highly impacts on neuronal network and cognitive capacity of large mammals. During development two important events shape the morphology of the cortex, the amplification of basal progenitors generating neurons, and the migration of the latter leading to the layered structure of the cortex. While amplification of basal progenitor cells represents a key event to induce gyration of the mammalian cortex, our knowledge on how neuronal migration and its lateral dispersion impacts cortex folding is scarce. Indeed, several studies have shown that migrating neurons in folded cortices have increased cellular dynamics, exploratory behaviour and lateral dispersion than those in the rodent brain with smooth surface, but the nature of this mechanism remains unknown. The problem can be broken down in several aspects: (i) genes: which molecules modulate lateral dispersion of migrating neurons, (ii) function: how lateral dispersion of neurons controls cortex folding. In this talk I will report on our research in understanding the relative contribution of cortical migration to folding of the mammalian cerebral cortex. I will exemplify this process by talking about how synaptic adhesion receptors are (re-)used during early cortical development to guide cortical migration and describe techniques to analyze intercellular adhesive and repulsive interactions.