Author/Authors :
Joseph، نويسنده , , Nancy M. and Mosher، نويسنده , , Jack T. and Buchstaller، نويسنده , , Johanna and Snider، نويسنده , , Paige and McKeever، نويسنده , , Paul E. and Lim، نويسنده , , Megan and Conway، نويسنده , , Simon J. and Parada، نويسنده , , Luis F. and Zhu، نويسنده , , Yuan and Morrison، نويسنده , , Sean J.، نويسنده ,
Abstract :
Summary
ibromatosis 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.
