Aberrant Growth and Differentiation of Oligodendrocyte Progenitors in Neurofibromatosis Type 1 Mutants
作者： Michael R. Bennett , Tilat A. Rizvi , Saikumar Karyala , Randall D. McKinnon , Nancy Ratner
DOI: 10.1523/JNEUROSCI.23-18-07207.2003
关键词:
摘要: Neurofibromatosis type 1 (NF1) patients are predisposed to learning disabilities, macrocephaly, and brain tumors as well abnormalities on magnetic resonance imaging that postulated result from abnormal myelination. Here we show Nf1 +/- spinal cords in adult mice have more than twofold-increased numbers of NG2+ progenitor cells. -/- embryonic increased Olig2+ progenitors. Also, cultures mutant embryos with hemizygous biallelic mutations dramatically CNS oligodendrocyte In medium allows growth neuroepithelial cells glial progenitors, hyper-respond FGF2, basal FGF-stimulated Ras-GTP, fail accumulate when treated a farnesyltransferase inhibitor. Cell accumulation results part proliferation decreased cell death. contrast wild-type cells, progenitors express the differentiation marker O4 while retaining expression nestin. also abnormally coexpress markers GFAP. Importantly, cord-derived which amplified 12-fold, retain ability form oligodendrocytes after vivo transplantation. The data reveal key role for neurofibromin Ras signaling maintenance pools suggest potential defects NF1 patients.
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