Item Details

title

THE ROLE OF FORKHEAD BOX Q1 IN EPIDERMAL HOMEOSTASIS

author

Roll, Matthew

abstract

The skin, or integumentary system, is a complex and crucial organ that protects the human body from variations in heat, loss of water over time, and serves as a barrier to physical, chemical, and biological insult. The skin has three main layers, the hypodermis, the dermis, and the epidermis. Of these layers, the epidermis serves as the arbiter of water loss and of barrier function and structure. This epidermal layer is classified as a squamous epithelium, consisting of layered cells known as keratinocytes. While there are other cell types that inhabit the epidermis, most cells in the epidermis are keratinocytes. Importantly, the keratinocytes of the epidermis have complex networks of signaling. From autocrine signaling to themselves, paracrine signaling to other keratinocytes of the same and separate layers and other cell types within the epidermis, and endocrine signaling to various distant sites, keratinocytes maintain these systems with rigid complicity. A salient point regarding these intracellular signaling pathways is that they are different within each layer, and in fact it has been found that each layer has at least one unique keratinocyte subset to integrate the complex signaling of the tissue. One such signaling pathway, that of calcium ion signaling, is known within the field as the organ and lineage specific factor which controls cell fate decisions of epidermal keratinocytes. It was found that calcium levels in the epidermis increase with the distance from the dermal-epidermal junction and that with impaired calcium sequestration and shuttling to the outer epidermis the functions of the epidermis are impaired, specifically. Herein, we identify a novel mechanism and a novel regulator of keratinocyte differentiation and proliferation. Forkhead box Q1, or FOXQ1, is a member of the forkhead box family of transcription factors. These factors range in function as activators and repressors of varied cellular and anatomical processes in all manner of cell types. FOXQ1 belongs to its own clade within the evolutionary map of Forkhead box proteins over time. It was found that FOXQ1 has disparate functions within different cell types in cancer, carcinomas versus melanomas, with its function in melanocytes and melanoma cells necessitating further study of this transcription factor within the complex tissue that is the epidermis. We report in this document evidence that supports the claim that FOXQ1 has a significant and central role in the integration of two very important signaling pathways within epidermal keratinocytes and plays an important role in regulating the differentiation and proliferation of epidermal keratinocytes.

subject

Differentiation

Epidermis

FOXQ1

Homeostasis

Integument

Proliferation

contributor

Nikiforov, Mikhail (advisor)

Soto-Pantoja, David (committee member)

Miller, Lance (committee member)

Kerr, Bethany (committee member)

date

2023-07-25T17:48:47Z (accessioned)

2023 (issued)

degree

Cancer Biology (discipline)

embargo

2028-05-13 (terms)

2028-05-13 (liftdate)

identifier

http://hdl.handle.net/10339/102282 (uri)

language

en (iso)

publisher

Wake Forest University

type

Dissertation