Abstract
Although the mechanisms that regulate development of the cerebral cortex have begun to emerge, in large part through the analysis of mutant mice (Boncinelli et al. 2000; Molnar and Hannan 2000; Walsh and Goffinet 2000), many questions remain unanswered. To provide resources for further dissecting cortical development, we have carried out a focused screen for recessive mutations that disrupt cortical development. One aim of the screen was to identify mutants that disrupt the tangential migration of interneurons into the cortex. At the same time, we also screened for mutations that altered the growth or morphology of the cerebral cortex. We report here the identification of thirteen mutants with defects in aspects of cortical development ranging from the establishment of epithelial polarity to the invasion of thalamocortical axons. Among the collection are three novel alleles of genes for which mutant alleles had already been used to explore forebrain development, and four mutants with defects in interneuron migration. The mutants that we describe here will aid in deciphering the molecules and mechanisms that regulate cortical development. Our results also highlight the utility of focused screens in the mouse, in addition to the large-scale and broadly targeted screens that are being carried out at mutagenesis centers.
Highlights
The cerebral cortex is the seat of consciousness and the means by which we carry out abstract reasoning
Other important insights have come from the study of spontaneous mutations that cause radial migration defects and lead to lissencephaly and similar cortical defects in humans
The expression of Dlx family homeodomain transcription factors is necessary for differentiation of neurons in the striatum and for migration of many, if not all, of the interneuron precursors that arise in the ganglionic eminences of the embryonic telencephalon (Marin and Rubenstein 2001, 2003)
Summary
The cerebral cortex is the seat of consciousness and the means by which we carry out abstract reasoning. Spontaneous mutations in mice such as reeler and scrambler have helped to tease apart the regulation of the radial migrations that create the cortical layers. Other important insights have come from the study of spontaneous mutations that cause radial migration defects and lead to lissencephaly and similar cortical defects in humans. Our understanding of radial migration and many other aspects of cortical development have benefited enormously from the application of gene knockout approaches in mice. Despite this progress, many aspects of cortical development remain to be explored and would benefit enormously from additional mutant resources. The tangential migrations of cortical interneurons, for example, are regulated differently from the radial migrations of projection neurons, and only a few mutations have been described that disrupt interneuron migration
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