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Cerebral Cortex Advance Access published online on March 2, 2006
Cerebral Cortex, doi:10.1093/cercor/bhj147
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Article

Reelin Induces the Detachment of Postnatal Subventricular Zone Cells and the Expression of the Egr-1 through Erk1/2 Activation

Sergi Simó 1, Lluís Pujadas 1, Miguel F. Segura 2, Anna La Torre 1, Jose A. Del Río 1, Jesús M. Ureña 1, Joan X. Comella 2, and Eduardo Soriano 1 *

1 Developmental Neurobiology and Regeneration Laboratory, Barcelona Science Park-IRB and Department of Cell Biology, University of Barcelona, E-08028 Barcelona, Spain
2 Cell Signaling and Apoptosis Group, Department of Basical Medical Sciences, University of Lleida and Hospital Universitari Arnau de Vilanova, E-25198 Lleida, Spain

* To whom correspondence should be addressed.
Eduardo Soriano, E-mail: esoriano{at}pcb.ub.es


  Abstract

Reelin binds to very low-density lipoprotein receptor and apolipoprotein E receptor 2, thereby inducing mDab1 phosphorylation and activation of the phosphatidylinositide 3 kinase (PI3K) pathway. Here we demonstrate that Reelin activates the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) pathway, which leads to the phosphorylation of Erk1/2 proteins. The inhibition of Src family kinases (SFK) blocked Reelin-dependent Erk1/2 activation. This was also shown in neuronal cultures from mDab1-deficient mice. Although rat sarcoma viral oncogene was weakly activated upon Reelin treatment, pharmacological inhibition of the PI3K pathway blocked Reelin-dependent ERK activation, which indicates cross talk between the ERK and PI3K pathways. We show that blockade of the ERK pathway does not prevent the chain migration of neurons from the subventricular zone (SVZ) but does inhibit the Reelin-dependent detachment of migrating neurons. We also show that Reelin induces the transcription of the early growth response 1 transcription factor. Our findings demonstrate that Reelin triggers ERK signaling in an SFK/mDab1- and PI3K-dependent manner and that ERK activation is required for Reelin-dependent transcriptional activation and the detachment of neurons migrating from the SVZ.

Keywords: ERK; neural migration; phosphorylation; signal transduction.
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