Chan, Chun-Hung; (2001) Development of the cerebral cortex: Emx genes and interneuron migration. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The homeobox genes Emx1 and Emx2 are mouse homologues of the Drosophila empty spiracles gene, which has been shown to be important in the development of the Drosophila nervous system. Previous studies have demonstrated the expression of Emx1 and Emx2 in overlapping regions of the developing forebrain, specifically in the neocortex and hippocampus. Emx2 is also expressed in parts of the ventral telencephalon, including the proliferative ventricular zone of the ganglionic eminence and amygdala. Recent evidence has shown that the vast majority of cortical interneurons are generated in the ganglionic eminence and migrate tangentially into the neocortex. The migration of these cortical interneurons is dependent upon the homeobox genes Dlx1 and Dlx2. The expression domain of Emx1 and Emx2 suggests a role in the development and regional patterning of the neocortex, and that Emx2 may also be involved in the generation and migration of cortical interneurons derived from the ganglionic eminence of the ventral telencephalon. Using a variety of techniques, including organotypic slice culture, in-situ hybridisation, and immunocytochemistry at the light and electron microscope levels, the present study examines the expression and function of Emx1 and Emx2 in the developing neocortex. In addition, using organotypic slice cultures, we investigated the tangential migration of neurons from the ganglionic eminence to the neocortex, and examined possible guidance cues involved in this mode of migration. The new findings of the present study can be summarised as follows: 1) Expression of Emx1 begins very early in embryonic life and continues through all stages of development to adulthood. This homeobox gene is expressed by cells containing the neurotransmitter glutamate, a marker of pyramidal neurons, and is absent from the majority of GABA-containing interneurons. Thus, the homeobox gene Emx1 can be reliably used as a marker of the pyramidal cell lineage. 2) Emx2 appears to be important in the migration of cortical interneurons from their site of origin in the ganglionic eminence. Lack of Emx2 results in disruptions in the tangential migration of these neurons. This defect appears to be time-dependent, and is more severe during the early stages of development. 3) The migration of interneurons from the ganglionic eminence to the neocortex follows strict migratory pathways, and utilises the fibres of the corticofugal system. The neural cell adhesion molecule TAG-1 mediates the interaction between the migrating neurons and the cortical efferent fibres. Studies during the last decade have documented the importance of a number of homeobox gene transcription factors in the development of the central nervous system. The present study provides new information about the expression of the Emx homeobox gene family in the developing rodent neocortex, and examines some functional roles for these genes in this system.

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