Understanding the molecular principles of nervous system connectivity is the biggest challenge in biomedical research for the XXIst century. Nervous system connectivity is regulated by two fundamental processes: cell migration and axon guidance. The cerebral cortex is the region of the brain that has undergone the biggest expansion in primates and is the responsible of our cognitive abilities. The mature cortex is formed by excitatory pyramidal neurons and inhibitory interneurons that arrive to the cortex by two different migratory pathways: radial migration and tangential migration, respectively. The so-called basal progenitor (BP) cells are especial pyramidal cell progenitors that increase the number of differentiated neurons and play a key function in increasing cortex size during primate evolution. In humans, mutations that affect neuron migration result in severe mental diseases. The characterization of these mutations has revealed many genes involved in cytoskeleton dynamics. Surprisingly, little is known about the extracellular factors that control neuron migration. Fibronectin and Leucine-Rich Transmembrane proteins (FLRT1-3) are expressed in the developing cortex and ventral telencephalon. My previous data revealed that FLRT2 and the axon guidance receptor Unc5D play a role in regulating the migration of the BP cells in the developing cortex of the mouse. In the present proposal I will use FLRTs as molecular entry points to analyze basic aspects of neuronal migration in the developing brain. I will address the exact mechanisms by which FLRT2 regulates the behaviour of the migrating BP cells and the contribution of FLRTs to the tangential migration of interneurons. I will also study the expression of FLRTs in human samples in order to extrapolate our observations to human cortex development and disease. The present proposal will provide novel molecular insights on neuron migration with a direct impact on human brain development, evolution and disease.