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Date of Award

Spring 5-15-2011

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Developmental, Regenerative, & Stem Cell Biology)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Hair shafts are produced from progenitor cells in the hair matrix that receive instructive signals from the dermal papilla to guide their differentiation. The molecular nature of this signal transduction is unclear. The homeodomain protein MSX2 is essential for epithelial-mesenchymal signal transduction during ectodermal appendage formation. In this study, we show that hair follicles FGF signaling is compromised in Msx2 mutant, as the expression of both FGF ligands(Fgf7 and Fgf10) as well astheir receptor (Fgfr2) is decreased in this mutant. Conditional removal of Fgfr2from the hair matrix led to a similar but less severe phenotype compared to Msx2 mutants, where the differentiation is affected in the cortex and medulla, but not cuticle of the hair shaft. Moreover, restoration of FGF signaling either in vitro or in vivo rescued Msx2 target gene expression and hair shaft differentiation. Finally, we uncovered a Bmp/Msx2/Fgfr2 linear genetic pathway that promotes the differentiation of matrix progenitor cells along the hair cortex and medulla lineages. Our data support a model in which continuous signal transduction between the matrix and the dermal papilla is required after cell-fate determination to ensure proper differentiation.

Language

English (en)

Chair and Committee

Whitney E. Purtha

Committee Members

Michael S. Diamond, Deepta Bhattacharya

Comments

Permanent URL: https://doi.org/10.7936/K7G73BVG

Available for download on Monday, December 15, 2110

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