Chapter 3 - Experimental Models of Cortical Malformations

Abstract

This chapter discusses various aspects of experimental models of cortical malformations. Malformations of cortical development such as hemimegalencephaly, lissencephaly, and polymicrogyria are important causes of mental retardation and epilepsy. X-linked lissencephaly and subcortical band heterotopia (XLIS) is a striking malformation syndrome that causes SBH in heterozygous (carrier) females and classical lissencephaly in hemizygous males. The Bilateral periventricular nodular heterotopia (BPNH) gene has been mapped to chromosome Xq28 in several of the multiplex families, but has not been cloned. Cobblestone lissencephaly is an unusual brain malformation characterized by agyria, pachygyria, or even polymicrogyria with a pebbled surface, white matter abnormalities, enlarged ventricles, and some other abnormalities such as hypoplasia of the brain stem and cerebellum. The gene has been mapped to a small region in chromosome 9q31 by linkage disequilibrium in Japanese families. The autosomal recessive mouse mutant reeler causes tremors, impaired motor coordination, and ataxia in affected mice. The gene responsible for the reeler phenotype was recently isolated and the protein product was named reelin. It is suggested that reelin serves as a neuron-to-matrix adhesion molecule that provides an extracellular cue to migrating neuroblasts to promote early organization of the cortex.