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SOX2 is known to activate expression of Six6, encoding a homeodomain transcription factor, in the ventral diencephalon. Here, we find that the same relationship likely exists in the pituitary. Moreover, because Six6 deletion is associated with a similar phenotype as described here for loss of Sox2, Six6 appears as an essential downstream target of SOX2 in the gland. We also uncover a second role for SOX2. While cell differentiation is reduced in Sox2 mutants, some endocrine cells are generated such as POMC positive cells in the intermediate lobe. However, loss of SOX2 here results in complete downregulation of the melanotroph pioneer factor PAX7, and subsequently a switch of identity from melanotrophs to ectopic corticotrophs. Rescuing proliferation by ablating the cell cycle negative regulator p27 in Sox2 mutants does not restore melanotroph emergence. Therefore SOX2 has two independent roles during pituitary morphogenesis, first promotion of progenitor proliferation, and subsequently acquisition of melanotroph identity.<\/jats:p>","DOI":"10.1242\/dev.137984","type":"journal-article","created":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T02:44:20Z","timestamp":1464230660000},"source":"Crossref","is-referenced-by-count":14,"title":["SOX2 is sequentially required for progenitor proliferation and lineage specification in the developing pituitary"],"prefix":"10.1242","author":[{"given":"Sam","family":"Goldsmith","sequence":"first","affiliation":[{"name":"The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9364-4179","authenticated-orcid":false,"given":"Robin","family":"Lovell-Badge","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0711-5452","authenticated-orcid":false,"given":"Karine","family":"Rizzoti","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042608304421300_DEV137984C1","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1242\/dev.02829","article-title":"Lack of the murine homeobox gene Hesx1 leads to a posterior transformation of the anterior forebrain","volume":"134","author":"Andoniadou","year":"2007","journal-title":"Development"},{"key":"2021042608304421300_DEV137984C2","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.stem.2013.07.004","article-title":"Sox2(+) stem\/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential","volume":"13","author":"Andoniadou","year":"2013","journal-title":"Cell Stem Cell"},{"key":"2021042608304421300_DEV137984C3","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1128\/MCB.01885-08","article-title":"Distinct developmental roles of cell cycle inhibitors p57Kip2 and p27Kip1 distinguish pituitary progenitor cell cycle exit from cell cycle reentry of differentiated cells","volume":"29","author":"Bilodeau","year":"2009","journal-title":"Mol. 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