C-met Induction in the Hippocampus of NF1-Null Mice

摘要

Children and mice with one defective NF1 allele have learning disabilities linked to hippocampal deficits. Compared to wild-type mice, expression of the c-met receptor tyrosine kinase is elevated in the hippocampus of mice with astrocyte-targeted disruption of the Nf1 gene. Hippocampal neurons from these mutant mice still express neurofibromin, arguing that increased c- met expression is not due to non-specific targeting of neurons. Both c-met and its ligand, hepatocyte growth factor, promote hippocampal neuron maturation and neuron sprouting. Here, the authors found that Nf1-null astrocytes do not induce c-met expression in wild-type hippocampal neurons in vitro, and that neurons from the mutant mice do not maintain elevated c-met expression in culture. However, they did find that mice with constitutively active K-ras mutations, but not mice with H-ras mutations, have elevated hippocampal c-met expression that is similar to that observed in the Nf1 mutant animals. Cell extrinsic factors may therefore influence how loss of neurofibromin in astrocytes regulates c-met expression by hippocampal neurons, and these effects may be dependent on K-ras signaling.