NOTCH activity differentially affects alternative cell fate acquisition and maintenance

eLife

Robin Lovell-Badge¹  Mathias Treier²  Paul Le Tissier³  Leonard Cheung⁴  Sam GJ Goldsmith⁵  Karine Rizzoti⁵ 

[1] Charité-Universitätsmedizin Berlin, Berlin, Germany;Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany;Centre for Discovery Brain Science, Integrative Physiology, Edinburgh, United Kingdom;Department of Human Genetics, University of Michigan, Ann Arbor, United States;The Francis Crick Institute, London, United Kingdom;

关键词: NOTCH signalling;    pituitary;    plasticity;   

DOI  :  10.7554/eLife.33318

来源: DOAJ

【 摘 要 】

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 Pou1f1-Cre; Rbpjfl/fl 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. Activation of NOTCH signalling in different cell lineages of the embryonic murine pituitary uncovers an unexpected differential sensitivity, and this consequently reveals new aspects of endocrine lineages development and plasticity.

【 授权许可】

Unknown