@article{231ed48711b54936b86e07ede2e523b0,
title = "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+Nf1fl/- 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.",
keywords = "CELLCYCLE, STEMCELL",
author = "Joseph, {Nancy M.} and Mosher, {Jack T.} and Johanna Buchstaller and Paige Snider and McKeever, {Paul E.} and Megan Lim and Conway, {Simon J.} and Parada, {Luis F.} and Yuan Zhu and Morrison, {Sean J.}",
note = "Funding Information: This work was supported by the NIH NINDS (R01 NS40750 to SJM) and the Howard Hughes Medical Institute. Generation of 3.9Periostin-Cre mice was supported by R01 HL077342 to S.J.C. and T32 HL079995 to P.S. Y.Z. was supported by grants from the American Cancer Society and Department of Defense. N.M.J was supported by an NRSA from the NINDS (F30 NS049761). J.T.M. was supported by the Aron Family NF Scholars Fellowship from the Children's Tumor Foundation. J.B. was supported by the Swiss National Science Foundation. Thanks to M. White and D. Adams for assistance with flow cytometry. Thanks to D. Sorensen for assistance with electron microscopy and to H. Zheng and L. Chang for assistance with P0aCre experiments. Thanks to Tyler Jacks for providing Nf1-deficient mice, to Karlyne Reilly for providing Nf1/p53 +/− cis mice, and to Ron DePinho for providing Ink4a and Ink4a/Arf mice. Thanks to Alan Saltiel's and Kun-Liang Guan's laboratories for advice related to western blots. Thanks to Michael Wegner, David Anderson, and Thomas Muller for providing antibodies against SoxE, Sox10, and BFABP. Thanks to Paul Cederna and Deborah Yu for advice with nerve injections. ",
year = "2008",
month = feb,
day = "5",
doi = "10.1016/j.ccr.2008.01.003",
language = "English (US)",
volume = "13",
pages = "129--140",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}