title: Cells of origin in the embryonic nerve roots for NF1-associated plexiform neurofibroma.
abstract: Neurofibromatosis type 1 is a tumor-predisposing genetic disorder. Plexiform neurofibromas are common NF1 tumors carrying a risk of malignant transformation, which is typically fatal. Little is known about mechanisms mediating initiation and identity of specific cell type that gives rise to neurofibromas. Using cell-lineage tracing, we identify a population of GAP43(+) PLP(+) precursors in embryonic nerve roots as the cells of origin for these tumors and report a non-germline neurofibroma model for preclinical drug screening to identify effective therapies. The identity of the tumor cell of origin and facility for isolation and expansion provides fertile ground for continued analysis to define factors critical for neurofibromagenesis. It also provides unique approaches to develop therapies to prevent neurofibroma formation in NF1 patients.
authors.affiliation: Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA.
authors.forename: Chiachi
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA; Cancer Biology Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA.
authors.forename: Amish J
authors.initials: AJ
authors.lastname: Patel
authors.affiliation: Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA.
authors.forename: Chung-Ping
authors.initials: CP
authors.lastname: Liao
authors.affiliation: Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA; Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA; UTSW Neurofibromatosis Clinic, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA. Electronic address: lu.le@utsouthwestern.edu.
authors.forename: Lu Q
authors.initials: LQ
authors.lastname: Le
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000473:pathology; D019070:Cell Lineage; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000473:pathology; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D005727:Ganglia, Spinal / Q000473:pathology; D008822:Mice, Transgenic; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D018318:Neurofibroma, Plexiform / Q000235:genetics / Q000473:pathology*; D025542:Neurofibromin 1 / Q000235:genetics*; D010524:Peripheral Nervous System Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D019922:GAP-43 Protein; D018991:Myelin Proteolipid Protein; D025542:Neurofibromin 1; C047516:Plp1 protein, mouse