Plexiform and dermal neurofibromas and pigmentation are caused by Nf1 loss in desert hedgehog-expressing cells

被引：171

作者：

Wu, Jianqiang ^{[1
]}

Williams, Jon P. ^{[1
]}

Rizvi, Tilat A. ^{[1
]}

Kordich, Jennifer J. ^{[1
]}

Witte, David ^{[2
]}

Meijer, Dies ^{[6
,7
]}

Stemmer-Rachamimov, Anat O. ^{[4
,5
]}

Cancelas, Jose A. ^{[1
,3
]}

Ratner, Nancy ^{[1
]}

机构：

[1] Univ Cincinnati, Coll Med,Div Expt Hematol & Canc Biol, Cincinnati Childrens Hosp Med Ctr, Cincinnati Childrens Res Fdn, Cincinnati, OH 45229 USA

[2] Univ Cincinnati, Coll Med,Div Pathol, Cincinnati Childrens Hosp Med Ctr, Cincinnati Childrens Res Fdn, Cincinnati, OH 45229 USA

[3] Univ Cincinnati, Coll Med,Hoxworth Blood Ctr, Cincinnati Childrens Hosp Med Ctr, Cincinnati Childrens Res Fdn, Cincinnati, OH 45229 USA

[4] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA

[5] Harvard Univ, Sch Med, Boston, MA 02129 USA

[6] Erasmus Univ, Ctr Med, Dept Cell Biol, NL-3000 DR Rotterdam, Netherlands

[7] Erasmus Univ, Ctr Med, Dept Genet, NL-3000 DR Rotterdam, Netherlands

来源：

CANCER CELL | 2008年 / 13卷 / 02期

关键词：

D O I：

10.1016/j.ccr.2007.12.027

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Neurofibromatosis type 1 (Nf1) mutation predisposes to benign peripheral nerve (glial) tumors called neurofibromas. The point(s) in development when Nf1 loss promotes neurofibroma formation are unknown. We show that inactivation of Nf1 in the glial lineage in vitro at embryonic day 12.5 + 1, but not earlier (neural crest) or later (mature Schwann cell), results in colony-forming cells capable of multilineage differentiation. In vivo, inactivation of Nf1 using a DhhCre driver beginning at E12.5 elicits plexiform neurofibromas, dermal neurofibromas, and pigmentation. Tumor Schwann cells uniquely show biallelic Nf1 inactivation. Peripheral nerve and tumors contain transiently proliferating Schwann cells that lose axonal contact, providing insight into early neurofibroma formation. We suggest that timing of Nf1 mutation is critical for neurofibroma formation. © 2008 Elsevier Inc. All rights reserved.

引用

页码：105 / 116

页数：12

共 48 条

[1] In vitro and in vivo differentiation of boundary cap neural crest stem cells into mature Schwann cells [J].