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First published online 3 October 2007
doi: 10.1242/dev.005447

Development 134, 3883-3891 (2007)
Published by The Company of Biologists 2007
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Divergent roles of ApoER2 and Vldlr in the migration of cortical neurons

Iris Hack1,*, Sabine Hellwig1,2,*, Dirk Junghans3, Bianka Brunne4, Hans H. Bock4, Shanting Zhao1 and Michael Frotscher1,4,{dagger}

1 Institut für Anatomie und Zellbiologie, Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg, Germany.
2 Neurologische Universitätsklinik, Neurozentrum, Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg, Germany.
3 Max-Planck-Institut für Immunbiologie, D-79108 Freiburg, Germany.
4 Zentrum für Neurowissenschaften, Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg, Germany.

{dagger} Author for correspondence (e-mail: Michael.Frotscher{at}anat.uni-freiburg.de)

Accepted 16 August 2007

Reelin, its lipoprotein receptors [very low density lipoprotein receptor (Vldlr) and apolipoprotein E receptor 2 (ApoER2; also known as Lrp8)], and the cytoplasmic adaptor protein disabled 1 (Dab1) are important for the correct formation of layers in the cerebral cortex. Reeler mice lacking the reelin protein show altered radial neuronal migration resulting in an inversion of cortical layers. ApoER2 Vldlr double-knockout mutants and Dab1 mutants show a reeler-like phenotype, whereas milder phenotypes are found if only one of the two lipoprotein receptors for reelin is absent. However, the precise role of the individual reelin receptors in neuronal migration remained unclear. In the study reported here, we performed fate mapping of newly generated cortical neurons in single and double receptor mutants using bromodeoxyuridine-labeling and layer-specific markers. We present evidence for divergent roles of the two reelin receptors Vldlr and ApoER2, with Vldlr mediating a stop signal for migrating neurons and ApoER2 being essential for the migration of late generated neocortical neurons.

Key words: Lipoprotein receptors, disabled 1, Reelin, Layer formation, Neuronal migration


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