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The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells.

Cancer cell | Feb 4, 2008

http://www.ncbi.nlm.nih.gov/pubmed/18242513

Neurofibromatosis is caused by the loss of neurofibromin (Nf1), leading to peripheral nervous system (PNS) tumors, including neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs). A long-standing question has been whether these tumors arise from neural crest stem cells (NCSCs) or differentiated glia. Germline or conditional Nf1 deficiency caused a transient increase in NCSC frequency and self-renewal in most regions of the fetal PNS. However, Nf1-deficient NCSCs did not persist postnatally in regions of the PNS that developed tumors and could not form tumors upon transplantation into adult nerves. Adult P0a-Cre+Nf1(fl/-) mice developed neurofibromas, and Nf1(+/-)Ink4a/Arf(-/-) and Nf1/p53(+/-) mice developed MPNSTs, but NCSCs did not persist postnatally in affected locations in these mice. Tumors appeared to arise from differentiated glia, not NCSCs.

Pubmed ID: 18242513 RIS Download

Mesh terms: Animals | Animals, Newborn | Cell Differentiation | Cell Proliferation | Gastrointestinal Tract | Intercellular Signaling Peptides and Proteins | Mice | Mutation | Myelin Sheath | Neoplasms | Nerve Sheath Neoplasms | Neural Crest | Neurofibroma, Plexiform | Neurofibromin 1 | Neuroglia | Peripheral Nervous System | Schwann Cells | Signal Transduction | Stem Cells | Tumor Suppressor Protein p53 | ras Proteins

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Associated grants

  • Agency: NINDS NIH HHS, Id: F30 NS049761
  • Agency: NHLBI NIH HHS, Id: R01 HL077342
  • Agency: NHLBI NIH HHS, Id: R01 HL077342
  • Agency: NHLBI NIH HHS, Id: R01 HL077342-04
  • Agency: NINDS NIH HHS, Id: R01 NS040750
  • Agency: NINDS NIH HHS, Id: R01 NS040750-01
  • Agency: NINDS NIH HHS, Id: R01 NS040750-06
  • Agency: NINDS NIH HHS, Id: R01 NS040750-07
  • Agency: NINDS NIH HHS, Id: R01 NS040750-08
  • Agency: NINDS NIH HHS, Id: R01 NS40750
  • Agency: NHLBI NIH HHS, Id: T32 HL079995

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