An organism's outermost covering, the integument, has evolved to fulfil a diverse range of functions. Skin provides a physical barrier, an environment for immunological surveillance, and also performs a range of sensory, thermoregulatory and biosynthetic functions. Examination of the skin of limb digits reveals a range of skin types including the thickened hairless epidermis of the toe pads (palmar or plantar epidermis) and thinner epidermis between the hair follicles (interfollicular epidermis) of hairy skin. An important developmental function of skin is to give rise to a diverse group of appendages including hair follicles, with associated sebaceous glands (or feathers and scales in chick), eccrine sweat glands and the nail. A key question is how does this morphological variety arise from the single-layered epithelium covering embryonic limb buds? This review will attempt to address this question by linking the extensive morphological /anatomical data on maturation of epidermis and its appendages with (1) current research into the range, plasticity and location of the putative epidermal stems cells; (2) molecular/microenvironmental regulation of epidermal stem cell lineages and lineage choice; and (3) regulation of the differentiation pathways, focusing on differentiation of the interfollicular epidermis.Key words appendages; cell lineages; ectoderm, skin barrier; skin development; terminal differentiation.
Epidermis as a structural barrier organNormal adult skin comprises a thin surface epidermis nourished and maintained by a thicker dermis. Epidermis of the limb gives rise to a range of skin types (palmar, plantar and interfollicular epidermis) and varied appendages (including hair follicles, sebaceous glands, eccrine sweat glands and the nail) (Fig. 1). Epidermis' primary role is protective and it provides protection largely through construction of an elaborate and highly organized outer surface, the stratum corneum. Stratum corneum is the primary interface and barrier between an organism and its outer environment and acts to prevent desiccation, toxin entry and microbial infection.A key feature of this protective outer layer is that it is continually shed and replenished by underlying keratinocytes, so that damaged, infected or contaminated cells are removed from the body and the barrier is maintained. The stem cells necessary for maintenance of this cycling structure are located in the basal stratum of epidermis ( Fig. 2) and in specialized compartments of skin appendages like hair follicles (see reviews by Fuchs & Raghavan, 2002;Watt, 2002). Proliferative keratinocytes (transit or transiently amplifying cells) derived from these stem cells also reside in this basal layer (see Stratum corneum consists of anucleate, flattened keratinocytes embedded in a lipid matrix ( Fig. 2; reviewed by Kalinin et al. 2001 The basement membrane separates the dermis (primarily consisting of fibroblasts, elastin and collagen) and the overlying epidermis. The epidermis comprises four distinct layers, basal, spino...