Autor: |
Emmerson E; Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States., May AJ; Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States., Nathan S; Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States., Cruz-Pacheco N; Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States., Lizama CO; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States., Maliskova L; Institute of Human Genetics, University of California, San Francisco, San Francisco, United States., Zovein AC; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States., Shen Y; Institute of Human Genetics, University of California, San Francisco, San Francisco, United States., Muench MO; Blood Systems Research Institute, San Francisco, United States., Knox SM; Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States. |
Abstrakt: |
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. |