Self-formation of functional adenohypophysis in three-dimensional culture
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- 9 November 2011
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 480 (7375), 57-62
- https://doi.org/10.1038/nature10637
Abstract
The adenohypophysis (anterior pituitary) is a major centre for systemic hormones. At present, no efficient stem-cell culture for its generation is available, partly because of insufficient knowledge about how the pituitary primordium (Rathke's pouch) is induced in the embryonic head ectoderm. Here we report efficient self-formation of three-dimensional adenohypophysis tissues in an aggregate culture of mouse embryonic stem (ES) cells. ES cells were stimulated to differentiate into non-neural head ectoderm and hypothalamic neuroectoderm in adjacent layers within the aggregate, and treated with hedgehog signalling. Self-organization of Rathke's-pouch-like three-dimensional structures occurred at the interface of these two epithelia, as seen in vivo, and various endocrine cells including corticotrophs and somatotrophs were subsequently produced. The corticotrophs efficiently secreted adrenocorticotropic hormone in response to corticotrophin releasing hormone and, when grafted in vivo, these cells rescued the systemic glucocorticoid level in hypopituitary mice. Thus, functional anterior pituitary tissue self-forms in ES cell culture, recapitulating local tissue interactions.Keywords
This publication has 32 references indexed in Scilit:
- Self-organizing optic-cup morphogenesis in three-dimensional cultureNature, 2011
- Birthdating studies reshape models for pituitary gland cell specificationDevelopmental Biology, 2011
- Lack of the ventral anterior homeodomain transcription factor VAX1 leads to induction of a second pituitaryDevelopment, 2011
- Molecular mechanisms of pituitary organogenesis: In search of novel regulatory genesMolecular and Cellular Endocrinology, 2010
- Genetic Regulation of Pituitary Gland Development in Human and MouseEndocrine Reviews, 2009
- The molecular basis of hypopituitarismTrends in Endocrinology & Metabolism, 2009
- Minimization of exogenous signals in ES cell culture induces rostral hypothalamic differentiationProceedings of the National Academy of Sciences, 2008
- Mechanisms underlying pituitary hypoplasia and failed cell specification in Lhx3-deficient miceDevelopmental Biology, 2007
- Initiation to end point: the multiple roles of fibroblast growth factors in neural developmentNature Reviews Neuroscience, 2007
- Sustained Notch signaling in progenitors is required for sequential emergence of distinct cell lineages during organogenesisGenes & Development, 2006