SOX2 regulates acinar cell development in the salivary gland

• Published in: eLife Vol. 6
• Main Authors: Emmerson, Elaine, May, Alison J, Nathan, Sara, Cruz-Pacheco, Noel, Lizama, Carlos O, Maliskova, Lenka, Zovein, Ann C, Shen, Yin, Muench, Marcus O, Knox, Sarah M
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 17.06.2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Ablation; Acinar cells; Acinar Cells - physiology; Animals; Cell Differentiation; Cell lineage; Cell regulation; Developmental Biology and Stem Cells; epithelial morphogenesis; Gene Knockout Techniques; Genetic aspects; Health aspects; Humans; Mice; Morphogenesis; Organogenesis; parasympathetic nerves; Parasympathetic nervous system; Peripheral nerves; Properties; Proteins; Rodents; Salivary gland; Salivary glands; Salivary Glands - cytology; Salivary Glands - embryology; SOX2; SOXB1 Transcription Factors - metabolism; Superoxide dismutase; United States > US; California; SOX2; mouse; stem cells; acinar cells; parasympathetic nerves; epithelial morphogenesis; developmental biology; organogenesis
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.26620

Acinar cells play an essential role in the secretory function of exocrine organs. Despite this requirement, how acinar cells are generated during organogenesis is unclear. Using the acini-ductal network of the developing human and murine salivary gland, we demonstrate an unexpected role for SOX2 and parasympathetic nerves in generating the acinar lineage that has broad implications for epithelial morphogenesis. Despite SOX2 being expressed by progenitors that give rise to both acinar and duct cells, genetic ablation of SOX2 results in a failure to establish acini but not ducts. Furthermore, we show that SOX2 targets acinar-specific genes and is essential for the survival of acinar but not ductal cells. Finally, we illustrate an unexpected and novel role for peripheral nerves in the creation of acini throughout development via regulation of SOX2. Thus, SOX2 is a master regulator of the acinar cell lineage essential to the establishment of a functional organ.