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Patients with NF1 present with a wide range of clinical manifestations, and the tumor with highest prevalence is cutaneous neurofibroma (cNF). Most patients harboring cNF suffer greatly from the burden of those tumors, which have no effective medical treatment. Ironically, none of the numerous NF1 mouse models developed so far recapitulate cNF. Here, we discovered that HOXB7 serves as a lineage marker to trace the developmental origin of cNF neoplastic cells. Ablating Nf1 in the HOXB7 lineage faithfully recapitulates both human cutaneous and plexiform neurofibroma. In addition, we discovered that modulation of the Hippo pathway acts as a \u201cmodifier\u201d for neurofibroma tumorigenesis. This mouse model opens the doors for deciphering the evolution of cNF to identify effective therapies, where none exist today.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>This study provides insights into the developmental origin of cNF, the most common tumor in NF1, and generates the first mouse model that faithfully recapitulates both human cutaneous and plexiform neurofibroma. The study also demonstrates that the Hippo pathway can modify neurofibromagenesis, suggesting that dampening the Hippo pathway could be an attractive therapeutic target.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 1<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-18-0151","type":"journal-article","created":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T09:49:11Z","timestamp":1540201751000},"page":"114-129","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Spatiotemporal Loss of\n                    <i>NF1<\/i>\n                    in Schwann Cell Lineage Leads to Different Types of Cutaneous Neurofibroma Susceptible to Modification by the Hippo Pathway"],"prefix":"10.1158","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6451-2265","authenticated-orcid":false,"given":"Zhiguo","family":"Chen","sequence":"first","affiliation":[{"name":"1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Mo","sequence":"additional","affiliation":[{"name":"1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Brosseau","sequence":"additional","affiliation":[{"name":"1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"Shipman","sequence":"additional","affiliation":[{"name":"1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Ping","family":"Liao","sequence":"additional","affiliation":[{"name":"1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7468-2062","authenticated-orcid":false,"given":"Jonathan M.","family":"Cooper","sequence":"additional","affiliation":[{"name":"1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3573-3565","authenticated-orcid":false,"given":"Robert 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Texas."},{"name":"5Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2817-5382","authenticated-orcid":false,"given":"Lu Q.","family":"Le","sequence":"additional","affiliation":[{"name":"1Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas."},{"name":"4Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas."},{"name":"5Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas."},{"name":"6Neurofibromatosis Clinic, The University of Texas Southwestern Medical Center, Dallas, 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