LIS1 functions in normal development and disease

Abstract

LIS1, the first gene to be identified as involved in a neuronal migration disease, is a dosage-sensitive gene whose proper levels are required for multiple aspects of cortical development. Deletions in LIS1 result in a severe brain malformation, known as lissencephaly, whereas duplications delay brain development. LIS1 affects the proliferation of progenitors, spindle orientation and interkinetic nuclear movement in the ventricular zone, as well as nucleokinesis and migration of neurons. LIS1 regulatory interaction with the minus end directed molecular motor cytoplasmic dynein is the key for understanding its complex cellular functions. LIS1-dynein interaction decreases the average velocity of the molecular motor in vitro, shows more complex effects in vivo, and may be of importance in high-load transport especially in neurons.