SOX2 is sequentially required for progenitor proliferation and lineage specification in the developing pituitary
journal contributionposted on 12.08.2020, 13:24 authored by Sam Goldsmith, Robin Lovell-Badge, Karine Rizzoti
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.
Cell fateMorphogenesisPituitaryProgenitorSOXAnimalsCell CountCell LineageCell ProliferationCorticotrophsCyclin-Dependent Kinase Inhibitor p27Down-RegulationGene DeletionGene Expression Regulation, DevelopmentalHomeodomain ProteinsMelanotrophsMice, Inbred C57BLModels, BiologicalPAX7 Transcription FactorPituitary GlandPro-OpiomelanocortinRNA, MessengerRepressor ProteinsSOXB1 Transcription FactorsStem CellsTrans-ActivatorsLovell-Badge FC001107LM-ackBRF-ack06 Biological Sciences11 Medical and Health Sciences