title: Induction of abnormal proliferation by nonmyelinating schwann cells triggers neurofibroma formation.
abstract: Recent evidence suggests that alterations in the self-renewal program of stem/progenitor cells can cause tumorigenesis. By utilizing genetically engineered mouse models of neurofibromatosis type 1 (NF1), we demonstrated that plexiform neurofibroma, the only benign peripheral nerve sheath tumor with potential for malignant transformation, results from Nf1 deficiency in fetal stem/progenitor cells of peripheral nerves. Surprisingly, this did not cause hyperproliferation or tumorigenesis in early postnatal period. Instead, peripheral nerve development appeared largely normal in the absence of Nf1 except for abnormal Remak bundles, the nonmyelinated axon-Schwann cell unit, identified in postnatal mutant nerves. Subsequent degeneration of abnormal Remak bundles was accompanied by initial expansion of nonmyelinating Schwann cells. We suggest abnormally differentiated Remak bundles as a cell of origin for plexiform neurofibroma.
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Huarui
authors.initials: H
authors.lastname: Zheng
authors.forename: Lou
authors.initials: L
authors.lastname: Chang
authors.forename: Neha
authors.initials: N
authors.lastname: Patel
authors.forename: Jiong
authors.initials: J
authors.lastname: Yang
authors.forename: Lori
authors.initials: L
authors.lastname: Lowe
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Burns
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D018450:Disease Progression; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D018390:Gene Targeting; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D009186:Myelin Sheath / Q000473:pathology*; D009455:Neurofibroma / Q000473:pathology*; D025542:Neurofibromin 1 / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D011995:Recombination, Genetic; D012583:Schwann Cells / Q000473:pathology*; D012584:Sciatic Nerve / Q000196:embryology / Q000473:pathology / Q000648:ultrastructure; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D025542:Neurofibromin 1; D020800:Receptor, Nerve Growth Factor; C045073:Cre recombinase; D019426:Integrases