Student Theses and Dissertations

Horace Rhee

Date of Award

2007

Document Type

Thesis

RU Laboratory

Fuchs Laboratory

Keywords

skin architecture, hair follicle stem cells, embryonic hair progenitors

Abstract

The skin epidermis develops from a single uniform layer of multipotent cells during embryogenesis. Morphogenesis of hair follicles is initiated when a series of reciprocal interactions between this undifferentiated ectoderm and its underlying mesenchyme leads to a localized invagination of epithelial cells. As hair follicle development proceeds, stem cells are specified and set aside to fuel the postnatal hair cycle and repair the epidermis after injury. Although many signaling pathways have been identified by genetic studies to be essential for the induction of hair follicle morphogenesis and differentiation, little is known about the downstream genetic targets and molecular mechanisms in specifying a hair cell fate and establishing the stem cell niche. To define how the embryonic epithelium is able to integrate signals to direct, maintain, and regulate the hair cell lineage, I developed a strategy to isolate and transcriptionally profile embryonic hair progenitors and interfollicular epidermis in mice. This screen not only substantiated genes previously implicated in hair and epidermal development, but also uncovered genes that could be important in orchestrating lineage specification of multipotent skin progenitors. Many of these uncharacterized genes were also differentially expressed in the stem cells of postnatal hair follicles, suggesting that embryonic hair progenitors may directly give rise to and reflect functional attributes of adult stem cells. To test this premise, I evaluated the role of transcription factor Lhx2 in skin development. Expressed specifically by both embryonic hair progenitors and postnatal follicle stem cells, Lhx2 functions to establish hair follicle stem cells and maintain their undifferentiated, quiescent state. Loss of Lhx2 reduces hair follicle number and causes stem cells to precociously differentiate, whereas gain of Lhx2 inhibits differentiation and promotes a hair follicle stem cell fate. Thus, Lhx2 appears to be a molecular link between the specification of embryonic hair progenitors and adult multipotent stem cells. Further characterization into genes that regulate hair follicle morphogenesis is expected to expand our understanding of how stem cells are established and maintained, and the potential mechanisms by which they are disrupted in skin disease.

Comments

A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy.

Permanent URL

http://hdl.handle.net/10209/138

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