Requirement and Function of Hippo Pathway Signaling in the Mammalian Gastrointestinal Tract: A Dissertation
Authors
Cotton, Jennifer L.Faculty Advisor
Junhao Mao, Ph.D.Academic Program
Cancer BiologyUMass Chan Affiliations
Molecular, Cell and Cancer Biology DepartmentDocument Type
Doctoral DissertationPublication Date
2016-10-21Keywords
Gastrointestinal TractNeoplastic Cell Transformation
Mesenchymal Stromal Cells
Phosphoproteins
Signal Transducing Adaptor Proteins
Transcription Factors
Protein-Serine-Threonine Kinases
Hippo Pathway
Mammals
Cancer Biology
Cell Biology
Developmental Biology
Metadata
Show full item recordAbstract
In cancer, aberrant activation of developmental signaling pathways such as the Hippo Pathway has been shown to drive proliferation and invasion of cancer cells. Therefore, understanding the normal function of the Hippo Pathway during embryonic development can provide critical insight into how aberrant activity contributes to tumorigenesis. This dissertation explores the role of the Hippo Pathway members YAP and TAZ in gastrointestinal (GI) development and tumorigenesis. I use mouse genetics to systematically dissect the roles of YAP/TAZ in the endoderm-derived gastrointestinal epithelia and mesoderm-derived gastrointestinal mesenchyme during mammalian development. In the GI epithelium, I demonstrate that YAP/TAZ are dispensable for development and homeostasis. However, YAP/TAZ are required for Wnt pathway-driven tumorigenesis. I find that YAP/TAZ are direct transcriptional targets of Wnt/TCF4 signaling. In the GI mesenchyme, I describe a previously unknown requirement for YAP/TAZ activity during mammalian GI development. YAP/TAZ are involved in normal GI mesenchymal differentiation and function as transcriptional co-repressors in a progenitor cell population. In this way, YAP/TAZ act as molecular gatekeepers prior to Hedgehog-mediated differentiation into smooth muscle cells. This work unveils a previously unknown requirement for Hippo pathway signaling in the mammalian GI tract and a novel mechanism wherein YAP/TAZ function as transcriptional co-repressors to maintain a mesenchymal progenitor cell population.DOI
10.13028/M24K54Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32242Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/M24K54