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The Role of Ectodermally Derived Epithelium in the Development, Maintenance, and Pathogenesis of Tissues and Structures in the Craniofacial Complex

  • Author(s): Jones, Kyle Burke
  • Advisor(s): Klein, Ophir D
  • et al.
Abstract

The craniofacial complex comprises myriad cells types, tissues, and anatomic structures, all of which are vital for proper function. Two of these tissues, the ectodermally derived epidermis and oral epithelium, play integral roles in the embryonic development of several important craniofacial structures, such as hair follicles, sweat glands, and minor salivary glands. They are also important for maintaining epidermal and oral mucosal barrier integrity. Dysfunction in the development and/or integrity of these tissues can lead to serious clinical sequelae. One of the key cell types within the epidermis and oral mucosa that is crucial to maintaining homeostasis is the epithelial stem cell. While much work has been done in the epidermis to identify and characterize these cells, there is still relatively little known about stem cells within the oral epithelium. For example, where in the oral epithelium are these cells located? How can they be identified? Are they rare or numerous? What role do these cells play in oral disease? Identifying and characterizing epithelial stem cells will be crucial to understanding how they maintain tissue homeostasis as well as the role they may play in the development of various diseases in the craniofacial complex. Furthermore, an increased understanding of their organization and biology could lead to new treatment strategies.

This dissertation is organized into two main sections. The first section (Chapter 2) focuses on the identification of oral epithelial stem cells and their organization within the adult mouse using basic science approaches and techniques. The second section (Chapters 3 and 4) centers on the clinical sequelae that result from presumed defects in epithelial stem cell function, specifically in the context of X-linked hypohidrotic ectodermal dysplasia and various intraoral white lesions. These basic science and clinical research studies together highlight the importance of epithelial stem cell biology in the development and maintenance of epithelial tissues within the craniofacial complex.

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