WNT SIGNALING AND HAIR FOLLICLE INITIATION

Dermis is required for structural integrity of the skin, and provides inductive cues for hair follicle initiation. Uniform Wnt signaling activity is present in dermal fibroblast precursors preceding hair follicle initiation, but the functional requirement of dermal Wnt signaling at early stages of skin differentiation and patterning remains largely uncharacterized. In my studies, I show that epidermal Wnt ligands are required for uniform dermal Wnt signaling/¿¿¿-catenin activity and regulate fibroblast cell proliferation and initiation of hair follicle placodes. In the absence of dermal Wnt signaling/¿¿¿-catenin activity, hair follicle formation is lost. Conversely, forced activation of ¿¿¿-catenin signaling leads to formation of thickened dermis, enlarged epidermal placodes and dermal condensates that result in prematurely differentiated enlarged hair follicles. These data reveal functional roles for dermal Wnt signaling/¿¿¿-catenin in fibroblast proliferation and in the hair follicle initiation program in the epidermis. Moreover, a variety of secreted factors were identified that are differentially expressed in the mutant dermal fibroblasts using RNA-seq technology, suggesting these factors might be required for hair follicle initiation. This study lays the groundwork for developing future treatments of hair loss diseases and generating functional skin equivalents for wounded patients.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Biology

Grantor dc:publisher

Case Western Reserve University School of Graduate Studies

Year dc:date

2013

Author dc:creator

• Chen, Demeng

Contributors dc:contributor

• Atit, Radhika
• Wills, Mark

• Developmental Biology
• Dermis
• mouse embryo
• fibroblasts
• hair follicle
• Wnt
• -catenin

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=case1355448596

OAI identifier oai:identifier

oai:etd.ohiolink.edu:case1355448596