{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:50:32Z","timestamp":1791298232758,"version":"4.1.0"},"reference-count":46,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["164126"],"award-info":[{"award-number":["164126"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Despite the importance of the RAS-RAF-MAPK pathway in normal physiology and disease of numerous organs, its role during pituitary development and tumourigenesis remains largely unknown. Here we show that the over-activation of the MAPK pathway, through conditional expression of the gain-of-function alleles BrafV600E and KrasG12D in the developing mouse pituitary, results in severe hyperplasia and abnormal morphogenesis of the gland by the end of gestation. Cell-lineage commitment and terminal differentiation are disrupted, leading to a significant reduction in numbers of most of the hormone-producing cells before birth, with the exception of corticotrophs. Of note, Sox2+ve stem cells and clonogenic potential are drastically increased in the mutant pituitaries. Finally, we reveal that papillary craniopharyngioma (PCP), a benign human pituitary tumour harbouring BRAF p.V600E also contains Sox2+ve cells with sustained proliferative capacity and disrupted pituitary differentiation. Together, our data demonstrate a critical function of the MAPK pathway in controlling the balance between proliferation and differentiation of Sox2+ve cells and suggest that persistent proliferative capacity of Sox2+ve cells may underlie the pathogenesis of PCP.<\/jats:p>","DOI":"10.1242\/dev.150490","type":"journal-article","created":{"date-parts":[[2017,5,16]],"date-time":"2017-05-16T00:10:23Z","timestamp":1494893423000},"source":"Crossref","is-referenced-by-count":41,"title":["MAPK pathway activation in the embryonic pituitary results in stem cell compartment expansion, differentiation defects and provides insights into the pathogenesis of papillary craniopharyngioma"],"prefix":"10.1242","author":[{"given":"S.","family":"Haston","sequence":"first","affiliation":[{"name":"Developmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Pozzi","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Carreno","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Manshaei","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Panousopoulos","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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