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Molecular and Cellular Biology, October 2006, p. 7103-7115, Vol. 26, No. 19
0270-7306/06/$08.00+0     doi:10.1128/MCB.00424-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cortical Migration Defects in Mice Expressing A-RAF from the B-RAF Locus

Guadalupe Camarero,1,{dagger} Oleg Yu Tyrsin,1,{dagger} Chaomei Xiang,1,{dagger} Verena Pfeiffer,1 Sandra Pleiser,1 Stefan Wiese,2 Rudolf Götz,1 and Ulf R. Rapp1*

Institut für Medizinische Strahlenkunde und Zellforschung, Bayerische Julius-Maximilians-Universität, Versbacher-Str. 5, D-97078 Würzburg, Germany,1 Institut für Klinische Neurobiologie, Bayerische Julius-Maximilians-Universität, Josef Schneider-Str. 11, D-97078 Würzburg, Germany2

Received 10 March 2006/ Returned for modification 4 May 2006/ Accepted 3 July 2006

We have previously shown that mice lacking the protein kinase B-RAF have defects in both neural and endothelial cell lineages and die around embryonic day 12 (E12). To delineate the function of B-RAF in the brain, B-RAFKIN/KIN mice lacking B-RAF and expressing A-RAF under the control of the B-RAF locus were created. B-RAFKIN/KIN embryos displayed no vascular defects, no endothelial and neuronal apoptosis, or gross developmental abnormalities, and a significant proportion of these animals survived for up to 8 weeks. Cell proliferation in the neocortex was reduced from E14.5 onwards. Newborn cortical neurons were impaired in their migration toward the cortical plate, causing a depletion of Brn-2-expressing pyramidal neurons in layers II, III, and V of the postnatal cortex. Our data reveal that B-RAF is an important mediator of neuronal survival, migration, and dendrite formation and that A-RAF cannot fully compensate for these functions.


* Corresponding author. Mailing address: Institut für Medizinische Strahlenkunde und Zellforschung, Universität Würzburg, Versbacher Str. 5, D-97078 Würzburg, Germany. Phone: 49 931 201 45141. Fax: 49 931 201 45835. E-mail: rappur{at}mail.uni-wuerzburg.de.

{dagger} These authors contributed equally to this work.


Molecular and Cellular Biology, October 2006, p. 7103-7115, Vol. 26, No. 19
0270-7306/06/$08.00+0     doi:10.1128/MCB.00424-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.







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