Date of Award

1-1-2015

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Biological Sciences

Content Description

1 online resource (xx, 213 pages) : color illustrations

Dissertation/Thesis Chair

Melinda Larsen

Committee Members

Albert Millis, Susan LaFlamme, Haijun Chen

Keywords

Cellular Polarity, Differentiation, Myoepithelium, Sjogren's Syndrome, Submandibular Salivary Gland, Submandibular gland, Salivary glands, Morphogenesis, Mice, Branching processes

Subject Categories

Cell Biology | Developmental Biology | Molecular Biology

Abstract

Organogenesis is the process by which tissues organize, gain considerable size, and undergo cellular differentiation or specialization to form fully functional organs. To study the processes involved in organogenesis of branched organs, the mouse submandibular salivary gland is frequently used as a model system, as it can undergo morphogenesis and differentiation and be genetically manipulated ex vivo. The mouse submandibular salivary gland undergoes a specific process of outgrowth and invagination known as branching morphogenesis which allows for the significant increase in gland size and complexity, as well as maximization of surface area for secretion of saliva. Surrounding the mouse submandibular salivary gland is a thin layer of specialized extracellular matrix known as the basement membrane that is critical for the continued growth and development of the gland. The basement membrane contains collagens, laminins, and several other structural proteins involved in the formation of a complex matrix to provide structural support and out-side-in signalling. The outer layer of polarized epithelial cells that contacts the basement membrane and participates in its synthesis later differentiates into myoepithelial cells. One of the proteins known to be required for maintenance of the epithelial cellular polarity is Par-1b, a member of the PAR family of proteins. Par-1b is maintained on the basal side of the outermost polarized epithelial cells in early development, and we have shown here that it is both necessary and sufficient to drive the localized organization of the basement membrane. We have also shown that Par-1b, acting downstream of the small GTPase Rac1, is required for the differentiation of the outermost polarized epithelial cells into contractile myoepithelial cells.

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