Journal
DEVELOPMENT
Volume 143, Issue 13, Pages 2376-2388Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.137984
Keywords
SOX; Cell fate; Morphogenesis; Pituitary; Progenitor
Categories
Funding
- UK Medical Research Council [U117512772]
- Francis Crick Institute [10107]
- National Institute of Biomedical Imaging and Bioengineering (NBIB NIH) Neurovascular Regeneration BRP [EB016629]
- Worldwide Cancer Research [13-1270]
- Medical Research Council [MC_U117562207] Funding Source: researchfish
- The Francis Crick Institute [10107, 10109] Funding Source: researchfish
- Worldwide Cancer Research [13-1270] Funding Source: researchfish
- MRC [MC_U117562207] Funding Source: UKRI
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Sox2 mutations are associated with pituitary hormone deficiencies and the protein is required for pituitary progenitor proliferation, but its function has not been well characterized in this context. 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 to be an essential downstream target of SOX2 in the gland. We also uncover a second role for SOX2. Whereas 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 (also known as Cdkn1b) in Sox2 mutants does not restore melanotroph emergence. Therefore, SOX2 has two independent roles during pituitary morphogenesis; firstly, promotion of progenitor proliferation, and subsequently, acquisition of melanotroph identity.
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