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

ABSTRACT: 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.

SUBMITTER: Joseph NM

PROVIDER: S-EPMC2566828 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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

Joseph Nancy M NM Mosher Jack T JT Buchstaller Johanna J Snider Paige P McKeever Paul E PE Lim Megan M Conway Simon J SJ Parada Luis F LF Zhu Yuan Y Morrison Sean J SJ

Cancer cell 20080201 2

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 pos ...[more]

PMID: 18242513

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