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Development of Organoids from Mouse Pituitary as In Vitro Model to Explore Pituitary Stem Cell Biology
Published on: February 25, 2022
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SOX2 is sequentially required for progenitor proliferation and lineage specification in the developing pituitary
Sam Goldsmith1, Robin Lovell-Badge2, Karine Rizzoti2
1The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Development (Cambridge, England)
|May 27, 2016
Summary
Sox2 is crucial for pituitary development, promoting progenitor proliferation and melanotroph cell identity. Loss of Sox2 leads to hormone deficiencies and altered cell differentiation, highlighting its dual role in pituitary morphogenesis.
Area of Science:
- Developmental biology
- Endocrinology
- Genetics
Background:
- Sox2 mutations cause pituitary hormone deficiencies.
- Sox2 is essential for pituitary progenitor proliferation.
- SOX2 activates Six6 expression in the ventral diencephalon.
Purpose of the Study:
- To characterize the function of SOX2 in pituitary development.
- To investigate the downstream targets of SOX2 in the pituitary.
- To elucidate the role of SOX2 in pituitary cell differentiation and identity.
Main Methods:
- Analysis of Sox2 mutants in pituitary development.
- Investigating the relationship between SOX2 and Six6.
- Examining the role of SOX2 in melanotroph and corticotroph differentiation.
- Assessing the impact of p27 ablation on melanotroph emergence in Sox2 mutants.
Main Results:
- Six6 is identified as an essential downstream target of SOX2 in the pituitary.
- Loss of SOX2 leads to reduced cell differentiation and altered endocrine cell types.
- SOX2 is required for PAX7 downregulation, which dictates melanotroph identity.
- SOX2 loss results in a switch from melanotrophs to ectopic corticotrophs.
- Restoring proliferation in Sox2 mutants does not rescue melanotroph development.
Conclusions:
- SOX2 plays two independent roles in pituitary morphogenesis: promoting progenitor proliferation and enabling melanotroph identity acquisition.
- Six6 is a key downstream mediator of SOX2's role in pituitary progenitor proliferation.
- SOX2 regulates cell fate decisions, specifically the differentiation of melanotrophs, by controlling PAX7 expression.
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