2. Hair and follicle morphology

The aim of this chapter is to enhance the knowledge of the complex anatomy and physiology

of the hair in a simple manner (Table 1) [2, 5].

Anagen Growth stage of hair follicle cycle

Telogen Resting stage of hair follicle cycle

Terminal hairs Large and pigmented hairs

Follicular dermal papilla (DP)

Kenogen Telogen follicle without club hair form

derived tissues

matrix

Catagen Regression and involution stage of hair follicle cycle

Exogen Active hair shaft shedding stage of hair follicle cycle

Club hair Fully keratinized, dead hair formed at telogen stage

Vellus hair Non-pigmented, and generally non-medullated; short hairs

and the insertion of arrector pili muscle

Lanugo hair Fine hairs on the fetus body; shed in utero or within the first weeks after birth

Hair matrix Consists of rapidly proliferating keratinocytes that move upwards to produce the hair shaft

Hair bulb Lowermost portion of the hair follicle, includes the follicular dermal papilla and the hair

Isthmus The lower portion of the upper part of hair follicle between the opening of the sebaceous gland

Onion-shaped portion of hair bulb surrounded by hair matrix cells, consists of mesenchymally

Figure 1. Diagram of an anagen follicle.

142 Hair and Scalp Disorders Hair and Scalp Disorders

In utero, type and distribution of each hair follicle over the entire body are determined. The genes that are expressed before the signs of hair follicle formation constitute the precise spacing and distribution of the follicles. The protein products of these genes are presented during the different phases of hair cycle, indicating that they are so important for the normal development and distribution of follicles as well as for the ongoing growth process [4, 5].

The initial "message" for the development of all types of skin appendages is from the dermal mesenchyme (stage 0) and hair follicle development begins with the accumulation of epithelial cells to form epithelial placode after the initial mesenchymal signals (stage 1). Thereafter, the epithelial placode expands and generates the primary hair germ (stage 2). The second signal arises from epithelial placode and constitutes a cluster of adjacent mesenchymal cells which later develops the dermal papilla (DP). The ultimate signal from this primitive dermal papilla to the epithelial placode cells indicates a rapid proliferation and differentiation. This consecutive signaling process finally leads to the production of the mature follicle.

In the second stage of development, hair germ elongates into a cord of epithelial cells and forms the hair peg (stages 3 and 4). It is surrounded by mesenchymal cells that eventually transformed to the fibrous sheath. Derived from the epithelial cells of the hair peg, hair matrix cells form the hair shaft and inner root sheath (IRS). Outer root sheath (ORS) generates two bulges along the side of the hair follicle, the proximal bulge serves as a reservoir for epithelial stem cells and the distal bulge evolves to sebaceous glands. During the development of bullous peg (stages 5–8), the hair bulb and the main cell layers of the mature hair follicle are also formed [2–4, 6].

Several molecular pathways, growth factors, proteins and genes play substantial roles for the development of the hair follicle. Canonical (β-catenin dependent) WNT (wingless-type integration site) signals are candidates for the initial dermal message, and it is believed that they precede other activators and regulators of appendage development. β-Catenin is the downstream mediator of WTN signaling. Activation of this β-catenin pathway seems to be essential for the epithelial ability of the hair follicle production [7].

Ectodysplasin (EDA) and its receptor (EDAR) are another important pathways involved in the placode stage of hair morphogenesis. The mouse EDAR mRNA is expressed in the epithelium before placode formation, and then becomes restricted to placodes, whereas the EDA mRNA is still expressed even after placode formation [3, 6, 8]. In the placode stage, activated WNT and EDAR control the localized accumulation of sonic hedgehog (SHH), which is essential for the downgrowth of the hair germ [2]. In contrast to EDA and EDAR, members of the bone morphogenic protein (BMP) family of secreted signaling molecules seem to be inhibitors of placode formation. The antagonist named Noggin neutralizes BMP activity via regulation of lymphoid enhancer factor 1 (LEF1) expression [4]. EDAR is necessary for placode development in primary hair follicles but not for induction of secondary hair follicles, which utilize signaling pathways that involve Noggin and SRY-box 18 (SOX18) expression within the dermal papilla [9, 10].

In summary, the formation of placodes in response to the first dermal signal involves activation of EDA/EDAR signaling in the epithelium, followed by epithelial WNT signaling, and subsequent activation of BMP signaling. The actions of EDA/EDAR and WNT promote placode formation, whereas BMP signaling represses placode fate in adjacent skin [6].

Human hair follicle morphogenesis occurs only once. Lanugo, vellus and terminal hairs follow the same basic architectural principles. The first "coat" that is formed is fine, long, variably pigmented lanugo hair, which is shed in an anterior to posterior wave during last trimester of gestation. A second coat of fine, shorter, unpigmented lanugo hair then grows in all areas except the scalp and is shed 3–4 months after birth. After these first two cycles, hair starts to grow in an asynchronous "mosaic" pattern rather than in waves [2].
