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First published online 28 August 2008
doi: 10.1242/dev.024778

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Temporal regulation of ephrin/Eph signalling is required for the spatial patterning of the mammalian striatum

¹ Université Libre de Bruxelles (U.L.B.), IRIBHM (Institute for Interdisciplinary Research), 808 Route de Lennik, B-1070 Brussels, Belgium.
² Karolinska Institute, Department of Cell and Molecular Biology, SE-171 77 Stockholm, Sweden.
³ Uppsala University, Department of Neuroscience, 75123 Uppsala, Sweden.

^* Author for correspondence (e-mail: pierre.vanderhaeghen{at}ulb.ac.be)

Accepted 12 August 2008

Brain structures, whether mature or developing, display a wide diversity of pattern and shape, such as layers, nuclei or segments. The striatum in the mammalian forebrain displays a unique mosaic organization (subdivided into two morphologically and functionally defined neuronal compartments: the matrix and the striosomes) that underlies important functional features of the basal ganglia. Matrix and striosome neurons are generated sequentially during embryonic development, and segregate from each other to form a mosaic of distinct compartments. However, the molecular mechanisms that underlie this time-dependent process of neuronal segregation remain largely unknown. Using a novel organotypic assay, we identified ephrin/Eph family members as guidance cues that regulate matrix/striosome compartmentalization. We found that EphA4 and its ephrin ligands displayed specific temporal patterns of expression and function that play a significant role in the spatial segregation of matrix and striosome neurons. Analysis of the striatal patterning in ephrin A5/EphA4 mutant mice further revealed the requirement of EphA4 signalling for the proper sorting of matrix and striosome neuronal populations in vivo. These data constitute the first identification of genes involved in striatal compartmentalization, and reveal a novel mechanism by which the temporal control of guidance cues enables neuronal segregation, and thereby the generation of complex cellular patterns in the brain.

Key words: Forebrain, Neuronal migration, Ephrin, Striatum, Guidance

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