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

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

Authors

  • Joseph NM
  • Mosher JT
  • Buchstaller J
  • Snider P
  • McKeever PE
  • Lim M
  • Conway SJ
  • Parada LF
  • Zhu Y
  • Morrison SJ

Journal

Cancer cell

Publication Data

February 4, 2008

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

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