Date of Award
Doctor of Philosophy (PhD)
Microbiology, Molecular Biology and Biochemistry
Leslie A. Leinwand
The microRNA-200 (miR-200) family is well known for preventing epithelial-to-mesenchymal transition in cancer. However, the targets and functions of this family in normal epithelial tissues remain unclear. This five-member microRNA (miRNA) family also presents a unique platform for studying miRNA-mediated regulation, as they share two nearly-identical seed sequences. The results presented within this dissertation establish a role for these miRNAs in governing hair follicle morphogenesis and fine-tuning cell specification by regulating cell adhesion, polarity, and signaling pathways. By directly ligating miRNAs to their targeted mRNA regions, numerous miR-200 family targets are identified, many of which are involved in the regulation of focal adhesions, actin cytoskeleton, cell cycle and Hippo/Yap signaling. In addition, the experiments presented within this dissertation show that members of the miR-200 family interact with some unique genes, but that they also frequently share targets. Mouse models for miR-200 over-expression and loss-of-function show that the miR-200 family regulates cell adhesion, polarity and reduces cell division, leading to precise cell fate specification and hair morphogenesis. These findings demonstrate that combinatorial targeting of many genes is critical for miR-200 family functions, and provide new insights into this family’s functions in the developing skin and hair follicle.
Hoefert, Jaimee Elizabeth, "Targets and Functions of the Microrna-200 Family in the Developing Skin and Hair Follicle" (2018). Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations. 78.