
doi: 10.1038/nn1898
pmid: 17396120
To define the role of the Raf serine/threonine kinases in nervous system development, we conditionally targeted B-Raf and C-Raf, two of the three known mammalian Raf homologs, using a mouse line expressing Cre recombinase driven by a nestin promoter. Targeting of B-Raf, but not C-Raf, markedly attenuated baseline phosphorylation of Erk in neural tissues and led to growth retardation. Conditional elimination of B-Raf in dorsal root ganglion (DRG) neurons did not interfere with survival, but instead caused marked reduction in expression of the glial cell line-derived neurotrophic factor receptor Ret at postnatal stages, associated with a profound reduction in levels of transcription factor CBF-beta. Elimination of both alleles of Braf, which encodes B-Raf, and one allele of Raf1, which encodes C-Raf, affected DRG neuron maturation as well as proprioceptive axon projection toward the ventral horn in the spinal cord. Finally, conditional elimination of all Braf and Raf1 alleles strongly reduced neurotrophin-dependent axon growth in vitro as well as cutaneous axon terminal arborization in vivo. We conclude that Raf function is crucial for several aspects of DRG neuron development, including differentiation and axon growth.
Cell Survival, 106002 Biochemie, 106013 Genetics, Gene Expression, Mice, Transgenic, Nerve Tissue Proteins, Transfection, Mice, Ganglia, Spinal, Nerve Growth Factor, Animals, Neurons, Afferent, 106013 Genetik, Cells, Cultured, Stem Cells, 106002 Biochemistry, 301114 Cell biology, Cell Differentiation, Exons, 106025 Neurobiology, Embryo, Mammalian, Axons, Rats, Mice, Inbred C57BL, Mutation, 301114 Zellbiologie, 106025 Neurobiologie, Signal Transduction
Cell Survival, 106002 Biochemie, 106013 Genetics, Gene Expression, Mice, Transgenic, Nerve Tissue Proteins, Transfection, Mice, Ganglia, Spinal, Nerve Growth Factor, Animals, Neurons, Afferent, 106013 Genetik, Cells, Cultured, Stem Cells, 106002 Biochemistry, 301114 Cell biology, Cell Differentiation, Exons, 106025 Neurobiology, Embryo, Mammalian, Axons, Rats, Mice, Inbred C57BL, Mutation, 301114 Zellbiologie, 106025 Neurobiologie, Signal Transduction
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