Cortical migration defects in mice expressing A-RAF from the B-RAF locus.
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.
Camarero
Guadalupe
G
Institut für Medizinische Strahlenkunde und Zellforschung, Bayerische Julius-Maximilians-Universität, Versbacher-Str. 5, D-97078 Würzburg, Germany.
Tyrsin
Oleg Yu
OY
Xiang
Chaomei
C
Pfeiffer
Verena
V
Pleiser
Sandra
S
Wiese
Stefan
S
Götz
Rudolf
R
Rapp
Ulf R
UR
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
D048491:Proto-Oncogene Proteins A-raf; D048493:Proto-Oncogene Proteins B-raf