title: Cortical migration defects in mice expressing A-RAF from the B-RAF locus.
abstract: 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-RAF KIN/KIN mice lacking B-RAF and expressing A-RAF under the control of the B-RAF locus were created. B-RAF KIN/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.
authors.affiliation: Institut für Medizinische Strahlenkunde und Zellforschung, Bayerische Julius-Maximilians-Universität, Versbacher-Str. 5, D-97078 Würzburg, Germany.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Camarero
authors.forename: Oleg Yu
authors.initials: OY
authors.lastname: Tyrsin
authors.forename: Chaomei
authors.initials: C
authors.lastname: Xiang
authors.forename: Verena
authors.initials: V
authors.lastname: Pfeiffer
authors.forename: Sandra
authors.initials: S
authors.lastname: Pleiser
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiese
authors.forename: Rudolf
authors.initials: R
authors.lastname: Götz
authors.forename: Ulf R
authors.initials: UR
authors.lastname: Rapp
mesh_terms: D000818:Animals; D016923:Cell Death; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002552:Cerebral Ventricles / Q000166:cytology / Q000473:pathology; D003712:Dendrites / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D005838:Genotype; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019579:Neocortex / Q000166:cytology / Q000473:pathology*; D048491:Proto-Oncogene Proteins A-raf / Q000378:metabolism*; D048493:Proto-Oncogene Proteins B-raf / Q000172:deficiency / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology
chemical_list: D048491:Proto-Oncogene Proteins A-raf; D048493:Proto-Oncogene Proteins B-raf