DCX and LIS1 function in radial and lateral neuronal migration in developing cerebral cortex

Date of Completion

January 2006


Biology, Neuroscience




Neuronal migration is a fundamental process in developing cerebral cortex. During embryonic development, progenitors are located in the neuroepithelium that surrounds the ventricular lumen in the telencephalon. Progenitors divide and give rise to postmitotic daughter neurons. These neurons migrate to form a stereotyped laminar and radial organization in the maturing cerebral cortex. To understand the molecular and cellular mechanism of neuronal migration is a crucial step in not only elucidating the biology of brain development, but also in gaining greater insight into the pathogenesis of human neurological diseases linked to cortical malformation such as mental retardation, epilepsy, dyslexia and schizophrenia. Two innovative studies presented in this thesis further our understanding of the function of Doublecortin (DCX) and Lissencephaly 1 (LIS1) protein molecules in neuronal migration. The first study combines in utero electroporation and RNA interference (RNAi)-medicated acute knockdown of DCX to reveal the definitive function of DCX in radial migration, a major neuronal migration pathway in developing cerebral cortex. Utilizing similar techniques with high degree of spatial control, the second study shows shared, distinct and interdependent roles of DCX and LIS1 in the lateral cortical stream (LCS), a migration route for cells that populate ventral telencephalon including the piriform cortex and amygdala. ^