Neuronal Migration During Brain Development

In the 1970’s Rakic, Sidman and co-workers in this Center defined the mechanisms of neuronal migration during development of the mammalian cerebral cortex (J. Comp.  Neurol., 1972; Science,  1974;  J. Comp. Neurol., 1973). Radial glial fibers were discovered and shown to be the major guides of neuronal migration. The research indicated that sequential generations of cells originating in the germinative ventricular zones migrated in waves along these fibers, and that ultimately migrating neurons generated earliest in development reside in the deepest layers in cerebral cortex and neurons generated later reside in progressively more superficial layers, resulting in a cortex that is generated in an “inside out” fashion. These observations set the stage for subsequent insights into the genesis of disorders of neuronal migration in the brains of individuals with mental retardation and developmental disabilities. Indeed, MRI studies now have shown that such disorders, largely invisible to CT scanning, are much more common than previously suspected and are associated not only with the major cognitive deficits of mental retardation but with a variety of more restricted forms of developmental disability. The groundbreaking work of Rakic and Sidman ultimately led to the search for the genes determining neuronal migration.  Current work on the molecular basis of neuronal migration and how the disruption of this process leads to disorders of cognitive function is the focus of a number of current IDDRC investigators including Corfas, Segal, and Walsh.