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NOTCH activity differentially affects pituitary endocrine cell fate acquisition and maintenance

Authors

  • L. Cheung
  • P. Le Tissier
  • S.G. Goldsmith
  • M. Treier
  • R. Lovell-Badge
  • K. Rizzoti

Journal

  • eLife

Citation

  • eLife 7: e33318

Abstract

  • The pituitary is an essential endocrine gland regulating multiple processes. Regeneration of endocrine cells is of therapeutic interest and recent studies are promising, but mechanisms of endocrine cell fate acquisition need to be better characterised. The NOTCH pathway is important during pituitary development. Here, we further characterise its role in the murine pituitary, revealing differential sensitivity within and between lineages. In progenitors, NOTCH activation blocks cell fate acquisition, with time-dependant modulation. In differentiating cells, response to activation is blunted in the POU1F1 lineage, with apparently normal cell fate specification, while POMC cells remain sensitive. Absence of apparent defects in mice further suggests no direct role for NOTCH signalling in POU1F1 cell fate acquisition. In contrast, in the POMC lineage, NICD expression induces a regression towards a progenitor-like state, suggesting that the NOTCH pathway specifically blocks POMC cell differentiation. These results have implications for pituitary development, plasticity and regeneration.


DOI

doi:10.7554/eLife.33318