Homeostatic and tumourigenic activity of SOX2+ pituitary stem cells is controlled by the LATS/YAP/TAZ cascade

• DOI: 10.7554/elife.43996
• Publication Date: 2019-03-26T13:01:02Z
• Authors: Emily J Lodge; Alice Santambrogio; John P Russell; Paraskevi Xekouki; Thomas S Jacques; Randy L Johnson; Selvam Thavaraj; Stefan R Bornstein; Cynthia Lilian An...
• Keywords: Ectopic expression

SOX2 positive pituitary stem cells (PSCs) are specified embryonically and persist throughout life, giving rise to all endocrine lineages. We have previously shown the activation of STK/LATS/YAP/TAZ signalling cascade in developing postnatal mammalian pituitary. Here, we investigate function this pathway during development regulation cell compartment. Through loss- gain-of-function genetic approaches, reveal that restricting YAP/TAZ is essential for normal organ size specification from SOX2+ PSCs. Postnatal deletion LATS kinases subsequent upregulation leads uncontrolled clonal expansion PSCs disruption their differentiation, causing formation non-secreting, aggressive tumours. In contrast, sustained expression YAP alone results capable differentiation devoid tumourigenic potential. Our findings identify LATS/YAP/TAZ as an component PSC physiology tumourigenesis.