Developing stratified epithelia: lessons from the epidermis and thymus

Abstract

Stratified squamous epithelial cells are found in a number of organs, including the skin epidermis and the thymus. The progenitor cells of the developing epidermis form a multi-layered epithelium and appendages, like the hair follicle, to generate an essential barrier to protect against water loss and invasion of foreign pathogens. In contrast, the thymic epithelium forms a three-dimensional mesh of keratinocytes that are essential for positive and negative selection of self-restricted T cells. While these distinct stratified epithelial tissues derive from distinct embryonic germ layers, both tissues instruct immunity, and the epithelial differentiation programs and molecular mechanisms that control their development are remarkably similar. In this review, we aim to highlight some of the similarities between the thymus and the skin epidermis and its appendages during developmental specification.

Figure 1. Schematic Representation of the Histology of the Skin and Thymus Epithelium

A) The skin epithelium is comprised of the interfollicular epidermis and contains epidermal appendages, such as the hair follicle. Multiple stratified layers of differentiated keratinocytes with different characteristics create an intricate barrier. B) The thymus is a bi-lobed organ that contains two major compartments of epithelial cells, the outer cortex (blue cells) and medulla (pink cells) that form a three-dimensional organ.

Figure 2. Model Of Skin Epithelium and Thymic Epithelium Development

A) Schematic illustrating the serial progression of epidermal keratinocytes from prekeratinocyte progenitor cells (preKC) to keratinocyte progenitor cells (KCp), which generate epidermal lineages, pilosebaceous progenitors and Merkel cells. B) Schematic illustrating thymic epithelial development. Bipotent thymic epithelial cells (bTECp) generate a progenitor that has greater cortical features (tTECp) that form cortical TEC progenitors (cTECp) and medullary TEC progenitors (mTECp). Both of these progenitors form immature and mature TECs of their lineage. Mature mTECs form Hassle’s corpuscles in their final differentiation step. Circular arrows represent self-renewal. Shared markers are illustrated at the bottom.

Figure 3. Comparison Of Skin and Thymic Epithelial Molecular Mechanisms

A) Common signaling pathways utilized by both the thymus rudiment and hair placode during morphogenesis are indicated in Red. B) Cell specification utilizes some common signaling pathways as morphogenesis. Signaling pathways important at specific stages are indicated. SC, stem cell. TA, transit amplifying cell. Diff, differentiated cell.