NEURONAL MIGRATION IN THE CEREBRAL CORTEX - OF MICE AND MEN

The neocortex is an evolutionarily advanced brain structure responsible for higher-order cognition. Across the mammalian clade, the neocortex has drastically expanded and complexified. One of the key processes of neocortical development, which defines the future structure of the neocortex, is neuronal migration. Defective neuronal migration is linked with several human neurodevelopmental disorders. At the moment, mouse is the dominant model organism in neurodevelopmental studies. Migration of cortical neurons is widely studied in mouse but poorly investigated in human due to the limited access to live human fetal tissue. Major differences observed between mouse and human models indicate that studying human brain development and neuronal migration, in particular, needs to be done in human systems. Here, we have established an experimental pipeline for studying various aspects of cortical neuronal migration in human fetal tissue. We compared mouse and human excitatory projection neurons migration and discovered that human projection neurons migrate longer distances with a lower motility index and more frequent pausing. We demonstrated that human projection neurons move more tortuously than mouse which might allow them to disperse laterally, and it might be a specific mode of migration adopted by excitatory projection neurons in the expanded and folded neocortex. Understanding the neuronal migration of different mammalian species is essential for a better understanding of human cortex formation in health and disease.