Abstract
Here, Cheung et al. use sophisticated tissue specific genetic ablation in pituitary cell lineages to uncover an unexpected differential sensitivity of NOTCH activation signalling pathway in different cell lineages during the embryonic murine pituitary development. These findings are important as they further demonstrate the importance of NOTCH pathway in progenitor differentiation during pituitary development and consequently reveals new aspects of endocrine lineages and plasticity. Further work on the molecular differences on cell specific lineages and cell fate acquisition will be important to fine tune the mechanisms that generate pituitary plasticity. Importantly it will be useful to understand if these mechanisms are maintained in adult pituitary stem cells upon endocrine challenges to maintain adult organ homeostasis.
Highlights
The pituitary is an essential endocrine gland that is closely associated with the hypothalamus, in the ventral diencephalon, which controls its hormonal secretions
SOX2 is present in all pituitary progenitors (Fauquier et al, 2008; Rizzoti et al, 2013), while NKX3.1 is expressed predominantly in those located in the dorsal pituitary, peaking at 12.5dpc (Treier et al, 1998) (Goldsmith et al, 2016)
Our experiments reveal an unexpected differential sensitivity to NOTCH Intracellular Domain (NICD) expression between lineages and, in consequence, provide a better understanding of the physiological role of the pathway during pituitary development
Summary
The pituitary is an essential endocrine gland that is closely associated with the hypothalamus, in the ventral diencephalon, which controls its hormonal secretions. Pituitary hormone deficiencies, either congenital (1 in 3500 to 10000 births) (Alatzoglou and Dattani, 2009) or acquired later in life, mostly caused by tumours or brain damage, are associated with significant morbidity. Others, have characterized a population of stem cells (SCs) in the mouse pituitary (Rizzoti et al, 2013) (Andoniadou et al, 2013). The differentiation of embryonic SC to generate endocrine cells has been demonstrated in vitro (Suga et al, 2011). It would be of therapeutic interest to utilize SCs to generate endocrine cells; the limited efficiency of current protocols highlights the requirement for improved characterization of the mechanisms of endocrine cell fate acquisition
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