Date of Award
Spring 5-15-2011
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
Recommended Citation
He, Zhenhua, "MSX2 Provides Competence to Matrix Cells to Respond to FGF Signaling During Hair Differentation" (2011). Arts & Sciences Electronic Theses and Dissertations. 501.
https://openscholarship.wustl.edu/art_sci_etds/501
Comments
Permanent URL: https://doi.org/10.7936/K7G73BVG