Trends in Neurosciences
ReviewEmx homeogenes and mouse brain development
Section snippets
Emx1 and Emx2 in the developing mouse embryo
The onset of expression of Emx genes during mouse development varies. Emx2 transcript can be detected in E8.0–E8.5 embryos, whereas Emx1 expression starts from E9.5 (17, 18). In mouse embryos, Emx genes are expressed predominantly in extended regions of the developing rostral brain, including the presumptive cerebral cortex, olfactory bulbs and olfactory epithelium. Although Emx2 is expressed both in dorsal and ventral telencephalon and hypothalamus, Emx1 mRNA is restricted to the dorsal
Emx2 and cortical development
Emx2 is one of the earliest dorsal markers for the developing cerebral cortex (Fig. 3). From E8.5, a signal is visible in anterior dorsal neuroectodermal regions of the embryo. By E9.5, the expression domain extends to the olfactory placodes, and is delimited by an anterior boundary, which overlaps that of Emx1, and a posterior one, which is located within the roof of the presumptive diencephalon. From E10.0 and during the formation of cerebral cortex, the mRNA for Emx2 is detectable only in
EMX2 function revealed by knockout mice and human schizencephalies
Analysis of Emx2−/− mice has confirmed and specified the hypothetical function of EMX2 (21, 32, 33). Emx2 null embryo brains have major disturbances and structural changes in the architecture of various regions, including cerebral cortex. In particular, olfactory bulbs that are reduced in size and altered patterning of the hippocampus with total absence of a dentate gyrus are observed. EMX2 seems to contribute to the size of the hippocampus, rather than to the specification of the hippocampal
Emx1 in the developing forebrain
At E9.5 the posterior boundary of the Emx1 expression domain in dorsal telencephalon is slightly anterior to that between presumptive di- and telencephalon (Fig. 3). As development continues, Emx1 is expressed in most cortical neurons, regardless of whether they are proliferating, migrating or differentiating. In the mature cerebral cortex, Emx1 is expressed in fully differentiated and organized neurons18. The transcript for Emx1 is therefore widely distributed across cerebral cortex (VZ, IZ
Concluding remarks
Genetic manipulation of Emx genes represents a powerful tool with which to study the developing brain and, in particular, the cerebral cortex. Any alteration that occurs in these processes is thought to be responsible for severe developmental defects and pathologies of the nervous system, as described above. Mutations in EMX target genes are likely to underlie a number of brain defects. Preliminary support for this idea includes the observation that the number of WNT1-immunoreactive neurons is
Acknowledgements
The authors’ thank Celia Leonor Pardini for help with illustrations, and Larry Wrabetz, Riccardo Brambilla and Andrew Collick for helpful comments and critical reading of the manuscript. The authors’ studies were supported by grants from the Armenise-Harvard Foundation.
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