12 - Cytoplasmic dynein and its regulators in neocortical development and disease

Abstract

A hallmark of mammalian evolution is the establishment of the cerebral neocortex, which allows for the extremely complex level of connectivity required for many higher order cognitive functions. Recently cytoplasmic dynein and its regulatory proteins, including Lis1 and Nde1, have been found to play a fundamental role in development of the neocortex. Human mutations in genes encoding cytoplasmic dynein or its regulatory factors are associated with a variety of malformations of cortical development such as lissencephaly and microcephaly. This chapter focuses on what is known about the role of cytoplasmic dynein during normal neocortical development, with an emphasis on studies in rodent models. The latter part of the chapter focuses on the neuropathology associated with human mutations in dynein-related genes that result in cortical malformations, with particular emphasis on recent work concerning NDE1-associated microcephaly.