%0 Journal Article
%T LIS1 and DCX: Implications for Brain Development and Human Disease in Relation to Microtubules
%A Orly Reiner
%J Scientifica
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/393975
%X Proper lamination of the cerebral cortex requires the orchestrated motility of neurons from their place of birth to their final destination. Improper neuronal migration may result in a wide range of diseases, including brain malformations, such as lissencephaly, mental retardation, schizophrenia, and autism. Ours and other studies have implicated that microtubules and microtubule-associated proteins play an important role in the regulation of neuronal polarization and neuronal migration. Here, we will review normal processes of brain development and neuronal migration, describe neuronal migration diseases, and will focus on the microtubule-associated functions of LIS1 and DCX, which participate in the regulation of neuronal migration and are involved in the human developmental brain disease, lissencephaly. 1. Introduction Defined cell polarization is the key for the function of multiple cell types in the body, for example, the gut epithelium and the neuroepithelium, which both display an apicobasal orientation. Neurons, which part of them are generated from neuroepithelial cells, are also highly polarized cells with two distinct main structures that emerge from the cell body: usually a thin single axon, which is the key for signal transmission, and multiple shorter dendrites, which are designed for signal reception. The basic polarity of neurons was first recognized by Ramon y Cajal, who studied and described the morphology of neurons more than one hundred years ago [1]. In the cerebral cortex, two major types of neurons were defined: the excitatory or the glutaminergic neurons which compose the majority of the neurons in the cerebral cortex, and the inhibitory or the GABAergic interneurons composing the minority of the neurons. These two types of neurons are born in physically distinct areas of the brain, therefore, they need to migrate, sometimes very long distances, to reach their final destinations (reviews [2¨C6]). Genetic mutations, which affect polarity regulation and processes of neuronal migration in the developing brain, result in a wide array of human diseases. The range of diseases includes on the more severe end brain malformations, such as the lissencephaly-pachygyria spectrum, which defines the variety of diseases that cause relative smoothness of the brain surface and includes lissencephaly (smooth brain surface), agyria (no gyri), and pachygyria (broad gyri). In other cases, the brain surface may appear normal, but neurons can be mislocalized, which will be defined as cortical dysplasia. The position and the extent of the heterotropic
%U http://www.hindawi.com/journals/scientifica/2013/393975/