Jennifer Kersigo1, Lintao Gu2,3, Linjing Xu2, Ning Pan1,4, Sarath Vijayakuma5, Timothy Jones5, Seiji B Shibata2, Bernd Fritzsch1,2, Marlan R Hansen2. 1. Department of Biology, University of Lowa, Lowa City, Lowa, U.S.A. 2. Department of Otolaryngology, University of Lowa, Lowa City, Lowa, U.S.A. 3. Decibel Pharmaceutical, Boston, Massachusetts, U.S.A. 4. Department of Special Education & Communication Disorders, University of Nebraska, Lincoln, Nebraska, U.S.A. 5. Department of Otolaryngology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China.
Abstract
OBJECTIVES: The objective was to explore the effect of the proneuronal transcription factor neurogenic differentiation 1 (Neurod1, ND1) on Schwann cells (SC) and schwannoma cell proliferation. METHODS: Using a variety of transgenic mouse lines, we investigated how expression of Neurod1 effects medulloblastoma (MB) growth, schwannoma tumor progression, vestibular function, and SC cell proliferation. Primary human vestibular schwannoma (VS) cell cultures were transduced with adenoviral vectors expressing Neurod1. Cell proliferation was assessed by 5-ethynyl-2'-deoxyuridine (EdU) uptake. STUDY DESIGN: Basic science investigation. RESULTS: Expression of Neurod1 reduced the growth of slow-growing but not fast-growing MB models. Gene transfer of Neurod1 in human schwannoma cultures significantly reduced cell proliferation in dose-dependent way. Deletion of the neurofibromatosis type 2 (Nf2) tumor-suppressor gene via Cre expression in SCs led to increased intraganglionic SC proliferation and mildly reduced vestibular sensory-evoked potentials (VsEP) responses compared to age-matched wild-type littermates. The effect of Neurod1-induced expression on intraganglionic SC proliferation in animals lacking Nf2 was mild and highly variable. Sciatic nerve axotomy significantly increased SC proliferation in wild-type and Nf2-null animals, and expression of Neurod1 reduced the proliferative capacity of both wild-type and Nf2-null SCs following nerve injury. CONCLUSION: Expression of Neurod1 reduces slow-growing MB progression and reduces human SC proliferation in primary VS cultures. In a genetic mouse model of schwannomas, we find some effects of Neurod1 expression; however, the high variability indicates that more tightly regulated Neurod1 expression levels that mimic our in vitro data are needed to fully validate Neurod1 effects on schwannoma progression. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E259-E270, 2021.
OBJECTIVES: The objective was to explore the effect of the proneuronal transcription factor neurogenic differentiation 1 (Neurod1, ND1) on Schwann cells (SC) and schwannoma cell proliferation. METHODS: Using a variety of transgenic mouse lines, we investigated how expression of Neurod1 effects medulloblastoma (MB) growth, schwannoma tumor progression, vestibular function, and SC cell proliferation. Primary human vestibular schwannoma (VS) cell cultures were transduced with adenoviral vectors expressing Neurod1. Cell proliferation was assessed by 5-ethynyl-2'-deoxyuridine (EdU) uptake. STUDY DESIGN: Basic science investigation. RESULTS: Expression of Neurod1 reduced the growth of slow-growing but not fast-growing MB models. Gene transfer of Neurod1 in humanschwannoma cultures significantly reduced cell proliferation in dose-dependent way. Deletion of the neurofibromatosis type 2 (Nf2) tumor-suppressor gene via Cre expression in SCs led to increased intraganglionic SC proliferation and mildly reduced vestibular sensory-evoked potentials (VsEP) responses compared to age-matched wild-type littermates. The effect of Neurod1-induced expression on intraganglionic SC proliferation in animals lacking Nf2 was mild and highly variable. Sciatic nerve axotomy significantly increased SC proliferation in wild-type and Nf2-null animals, and expression of Neurod1 reduced the proliferative capacity of both wild-type and Nf2-null SCs following nerve injury. CONCLUSION: Expression of Neurod1 reduces slow-growing MB progression and reduces human SC proliferation in primary VS cultures. In a genetic mouse model of schwannomas, we find some effects of Neurod1 expression; however, the high variability indicates that more tightly regulated Neurod1 expression levels that mimic our in vitro data are needed to fully validate Neurod1 effects on schwannoma progression. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E259-E270, 2021.
Authors: Jeffrey R Gehlhausen; Su-Jung Park; Ann E Hickox; Matthew Shew; Karl Staser; Steven D Rhodes; Keshav Menon; Jacquelyn D Lajiness; Muithi Mwanthi; Xianlin Yang; Jin Yuan; Paul Territo; Gary Hutchins; Grzegorz Nalepa; Feng-Chun Yang; Simon J Conway; Michael G Heinz; Anat Stemmer-Rachamimov; Charles W Yates; D Wade Clapp Journal: Hum Mol Genet Date: 2014-08-11 Impact factor: 6.150
Authors: J A Trofatter; M M MacCollin; J L Rutter; J R Murrell; M P Duyao; D M Parry; R Eldridge; N Kley; A G Menon; K Pulaski Journal: Cell Date: 1993-03-12 Impact factor: 41.582
Authors: Scott R Plotkin; Anne C Albers; Dusica Babovic-Vuksanovic; Jaishri O Blakeley; Xandra O Breakefield; Courtney M Dunn; D Gareth Evans; Michael J Fisher; Jan M Friedman; Marco Giovannini; David H Gutmann; Michel Kalamarides; Andrea I McClatchey; Ludwine Messiaen; Helen Morrison; David B Parkinson; Anat O Stemmer-Rachamimov; Catherine D Van Raamsdonk; Vincent M Riccardi; Tena Rosser; Aaron Schindeler; Miriam J Smith; David A Stevenson; Nicole J Ullrich; Thijs van der Vaart; Brian Weiss; Brigitte C Widemann; Yuan Zhu; Annette C Bakker; Alison C Lloyd Journal: Am J Med Genet A Date: 2014-09-24 Impact factor: 2.802
Authors: Karen L Elliott; Gabriela Pavlínková; Victor V Chizhikov; Ebenezer N Yamoah; Bernd Fritzsch Journal: Int J Mol Sci Date: 2021-04-18 Impact factor: 5.923
Authors: Karen L Elliott; Jennifer Kersigo; Jeong Han Lee; Ebenezer N Yamoah; Bernd Fritzsch Journal: Front Neurol Date: 2021-12-16 Impact factor: 4.003