Cell Adhesion in Epidermal Development and Barrier Formation

doi:10.1016/bs.ctdb.2014.11.027

Current Topics in Developmental Biology

Volume 112, 2015, Pages 383-414

https://doi.org/10.1016/bs.ctdb.2014.11.027 Get rights and content

Abstract

Cell–cell adhesions are necessary for structural integrity and barrier formation of the epidermis. Here, we discuss insights from genetic and cell biological studies into the roles of individual cell–cell junctions and their composite proteins in regulating epidermal development and function. In addition to individual adhesive functions, we will discuss emerging ideas on mechanosensation/transduction of junctions in the epidermis, noncanonical roles for adhesion proteins, and crosstalk/interdependencies between the junctional systems. These studies have revealed that cell adhesion proteins are connected to many aspects of tissue physiology including growth control, differentiation, and inflammation.

Introduction

Cell–cell adhesion is essential for the formation and maintenance of multicellular tissues, particularly epithelia. Adhesion is provided by specialized cell–cell junctions, primarily adherens junctions (AJ), desmosomes, and tight junctions. In addition to forming physical connections between cells, these junctions organize and regulate cytoskeletal elements and modulate signaling pathways to regulate tissue development, structure, and physiology. Although cell adhesion has been extensively studied in cultured cells, genetic approaches have revealed the underlying physiologic functions of individual components and unexpected noncanonical roles of junctional proteins. Junctions do not function independently and it is becoming increasingly apparent that junctional crosstalk, interdependencies, and compensation are necessary for tissue robustness.

The mouse epidermis is a prime model to study the roles of cell–cell junctions in tissue architecture and physiology. The epidermis is a stratified epithelium that performs several essential protective functions. It is specialized to protect from water loss, dehydration, and toxin entry into the body. To accomplish this, the epidermis must form and maintain a tight barrier between the organism and its environment and withstand large amounts of mechanical stress on a daily basis. Essential to this barrier function is the proper establishment of cell–cell adhesion. Here, we discuss the roles for cell–cell adhesion in epidermal development and barrier function. Rather than a comprehensive review of the field, we have selected various new and under-discussed aspects of epidermal adhesion in addition to a basic description of roles of cell adhesion molecules in the epidermis elucidated by genetic studies.

Section snippets

Development of the Stratified Epidermis

The mouse epidermis is derived from surface ectoderm positioned atop a basement membrane that commits itself to an epidermal cell fate around embryonic day 9.5 (e9.5). Expression of the transcription factor p63, a master regulator of epidermal commitment, is required for the conversion from keratin 8/18-positive ectoderm to keratin 5/14-positive epidermis (Byrne et al., 1994, Mills et al., 1999, Pellegrini et al., 2001, Yang et al., 1999). This newly committed layer of cells becomes the basal

Adherens Junctions

AJs are cadherin-based junctions that link the F-actin cytoskeleton to the plasma membrane. Transmembrane cadherins, most prominently E-cadherin in the epidermis, form the physical linkages between cells through both lateral dimerization on the same cell and adhesion dimerization between E-cadherin molecules on adjacent cells (Brieher et al., 1996, Ozawa, 2002, Tomschy et al., 1996). The E-cadherin cytoplasmic tail binds the Armadillo repeat-containing proteins β-catenin and p120-catenin.

Desmosomes

Like AJs, desmosomes form around transmembrane cadherin molecules. There are two types of desmosomal cadherins, desmocollins and desmogleins. Mice and humans express three desmocollin genes and four desmoglein genes, which are expressed in cell-type specific manners. The cytoplasmic face of the desmosome contains two distinct electron-dense structures, called the outer-dense plaque and inner-dense plaque. The outer-dense plaque, in which plakoglobin and plakophilins bind the desmosomal cadherin

Tight Junctions

Unlike AJs and desmosomes, tight junctions are not cadherin-based adhesion structures. Rather, the predominant transmembrane protein components of these junctions are claudins and occludin. Both claudins and occludin have four transmembrane passes, though they are not structurally related beyond that. While occludin is not required for the formation of tight-junction strands, it has complex roles in their function. Claudins, in contrast, are necessary to form the strands of the tight junction (

Junctional Crosstalk in Epidermal Function

It is becoming increasingly clear that proper epidermal function requires the integration of all cell–cell adhesion systems and their associated cytoskeletons. This network of cell–cell adhesion systems that sense and respond to stress allows for tissue strengthening and full barrier function. We propose a model for how collaboration between these three elements is required for full barrier and mechanical strength of the granular layer of the epidermis (Fig. 2). The upregulation of cell–cell

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Chapter Twelve - Cell Adhesion in Epidermal Development and Barrier Formation

Abstract

Introduction

Section snippets

Development of the Stratified Epidermis

Adherens Junctions

Desmosomes

Tight Junctions

Junctional Crosstalk in Epidermal Function

Journal of Investigative Dermatology

Journal of Investigative Dermatology

American Journal of Human Genetics

Journal of Biological Chemistry

Developmental Biology

European Journal of Cell Biology

Current Opinion in Cell Biology

Cancer Letters

Cell Stem Cell

Cell

Journal of Biological Chemistry

Cell

Current Biology

Gastroenterology

Cell

Journal of Investigative Dermatology

Cell

Journal of Biological Chemistry

European Journal of Cell Biology

Journal of Ultrastructure Research

Cell

Journal of Biological Chemistry

Differentiation

Journal of Investigative Dermatology

European Journal of Cell Biology

Seminars in Cell & Developmental Biology

Journal of Biological Chemistry

Journal of Biological Chemistry

Journal of Biological Chemistry

Journal of Investigative Dermatology

Experimental Cell Research

Journal of Biological Chemistry

Journal of Investigative Dermatology

Journal of Investigative Dermatology

Journal of Biological Chemistry

Cell

Journal of Investigative Dermatology

Journal of Biological Chemistry

EPLIN mediates linkage of the cadherin catenin complex to F-actin and stabilizes the circumferential actin belt

Proceedings of the National Academy of Sciences of the United States of America

Assembly of the cadherin–catenin complex in vitro with recombinant proteins

Journal of Cell Science

Autoimmune and infectious skin diseases that target desmogleins

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences

p38MAPK inhibition prevents disease in pemphigus vulgaris mice

Proceedings of the National Academy of Sciences of the United States of America

Expression and localization of tight junction-associated proteins in human hair follicles

Archives of Dermatological Research

Suprabasal Dsg2 expression in transgenic mouse skin confers a hyperproliferative and apoptosis-resistant phenotype to keratinocytes

Journal of Cell Science

Lateral dimerization is required for the homophilic binding activity of C-cadherin

Journal of Cell Biology

Programming gene expression in developing epidermis

Development

Tight junction properties change during epidermis development

Experimental Dermatology

Loss of desmocollin 3 in mice leads to epidermal blistering

Journal of Cell Science

Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation

Journal of Cell Biology

Changing neighbours, changing behaviour: Cell adhesion molecule-mediated signalling during tumour progression

EMBO Journal