Characterization of oral mucosal neural crest and mesoderm-derived connective tissue cells

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General program goals and background****Cell interactions that lead to tooth formation are well understood but the processes involved in the development of oral mucosal gingivaan anatomically, histologically and functionally distinct part of oral mucosa that is in close contact with teethhave received little attention. Several studies have suggested that gingival connective tissue is composed of phenotypically distinct fibroblast subpopulations, but their identity has remained ambiguous. Interestingly, recent findings from our and other laboratories have indicated that gingival connective tissue cell subsets may derive from neural crest (NC) and mesoderm during development. Thus, the phenotypic heterogeneity of gingival fibroblast subpopulations may be determined by their developmental origin. We believe that gingiva provides an easily accessible source to study the fundamental properties of NC and mesoderm-derived cell subpopulations. Our general long-term goal is to identify and characterize these fibroblast subpopulations in gingiva and also use this information to understand the phenotype of fibroblast subsets in other tissues.*******General hypothesis****Our general hypothesis is that normal adult gingiva contains NC and mesoderm-derived fibroblast subpopulations that have distinct properties. Once identified and characterized, these cells can be used to find novel markers for the characterization and prospective isolation of similar subpopulations from various other tissues.*******General objectives and methods****Our general long-term goal is to identify and localize NC and mesoderm-derived connective tissue cells in normal gingiva based on immunoreactivity to distinct lineage markers and by using NC- and mesoderm-specific gene reporter mice. These cell subpopulations will then be isolated from human and reporter-mouse gingiva by immunological and other techniques and used to unravel their phenotype with proteomics tools, functional assays and gene expression analyses, and to uncover novel NC- and mesoderm-specific cell markers.*******Expected outcomes, significance and impact****These basic research approaches will identify and characterize in detail NC and mesoderm-derived cells in normal human and mouse gingiva for the first time, and uncover novel indicators that can be used to identify and isolate NC and mesoderm-derived cells in various tissues. This is relevant to our understanding of the processes involved in connective tissue development in general and its normal function post-development.***