Abstract
The pituitary gland is a primary endocrine organ that controls major physiological processes. Abnormal development or homeostatic disruptions can lead to human disorders such as hypopituitarism or tumors. Multiple signaling pathways, including WNT, BMP, FGF, and SHH regulate pituitary development but the role of the Hippo-YAP1/TAZ cascade is currently unknown. In multiple tissues, the Hippo kinase cascade underlies neoplasias; it influences organ size through the regulation of proliferation and apoptosis, and has roles in determining stem cell potential. We have used a sensitive mRNA in situ hybridization method (RNAscope) to determine the expression patterns of the Hippo pathway components during mouse pituitary development. We have also carried out immunolocalisation studies to determine when YAP1 and TAZ, the transcriptional effectors of the Hippo pathway, are active. We find that YAP1/TAZ are active in the stem/progenitor cell population throughout development and at postnatal stages, consistent with their role in promoting the stem cell state. Our results demonstrate for the first time the collective expression of major components of the Hippo pathway during normal embryonic and postnatal development of the pituitary gland.
Highlights
The pituitary gland is a critical endocrine organ that controls multiple essential physiological processes such as metabolism, stress response, growth and reproduction
Expression of Sox2 is known to be downregulated in committed lineages of the pituitary gland, which we confirmed at 13.5dpc; there is an absence of transcripts in the ventral anterior pituitary where cells are undergoing commitment (Figure 1F, asterisk)
In this manuscript we reveal that the Hippo signaling cascade is active during all stages of embryonic pituitary development assessed and continues to act in the postnatal organ
Summary
The pituitary gland is a critical endocrine organ that controls multiple essential physiological processes such as metabolism, stress response, growth and reproduction. The definitive pouch retains a central lumen that is lined by SOX2+ uncommitted progenitor cells (de Moraes et al, 2012; Rizzoti, 2015) Descendants of these SOX2+ cells restrict their fate to three lineages (Fauquier et al, 2008; Andoniadou et al, 2013; Rizzoti et al, 2013), which are characterized by expression of transcription factors PIT1, TPIT, and SF1. YAP1/TAZ is strongly associated with the stem cell state In this manuscript we have analyzed in detail the expression of components of the Hippo pathway in the developing pituitary gland and demonstrate its activity in SOX2+ cells during embryonic and postnatal development
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