Author

Philip Owens

Date

September 2008

Document Type

Dissertation

Degree Name

Ph.D.

Department

Dept. of Cell and Developmental Biology

Institution

Oregon Health & Science University

Abstract

Smad4 is at the nexus of many important cell signaling paradigms. The function of Smad4 has been to relay phosphorylated signals from the plasma membrane and shuttle them towards specific regions of DNA to elicit distinct transcriptional programs. These programs can mediate cellular fate, survival, migration, apoptosis and homeostasis. Smad4 was originally identified as a tumor suppressor in the pancreas over ten years ago, but since that time it has been found to be important in every cell type investigated as well as a critical mediator for normal differentiation and development. This thesis explores how Smad4 functions in skin. Conditionally removing this gene in skin helps determine its role during normal skin development, cutaneous wound healing and cancer. I have found that Smad4 is required for the proper differentiation of the hair follicle by its specific production of normal adhesions through the novel desmosomal cadherin Desmoglein-4 (Dsg4). Furthermore, I have found that deletion of Smad4 in the epidermis during cutaneous wound healing produces more profound cell non-autonomous defects than defects in Smad4-deficient keratinocytes. Additionally, the defects found in cutaneous wound healing mirror the tumorigenic processes that occur in spontaneous tumors formed in Smad4-deficient skin.

Identifier

doi:10.6083/M49021RN

School

School of Medicine

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