Epidermal-Dermal Signaling during Embryonic Hair Follicle Morphogenesis
Despite their differences, epidermal appendages, including mammalian hair follicles or avian feathers, share a similar developmental programme. A reciprocal exchange of inductive cues occurs between mid-gestation ectoderm and mesenchyme, to determine where these structures will form and trigger their initial development (Fig. 2).
Figure 2. Initiation of embryonic and adult anagen hair follicle development proceeds through inductive epidermal-mesenchymal signals: Embryonic dermis instructs overlying ectoderm to initiate placode formation, a structure which signals to mesenchymal fibroblasts to form dermal condensate. Subsequently, the dermal condensate signals to follicular keratinocytes to stimulate proliferation and downgrowth into developing dermis. The dermal condensate will be enrobed by epithelial cells and mature to form dermal papilla. Proliferating hair progenitors (matrix cells) that are pushed away from contacting the dermal papilla will differentiate in response to lateral signaling between keratinocytes into the 6 epithelial cell types making up the hair shaft. Shh is expressed in early placode and remains expressed at the distal tip of developing follicles. Adult hair follicles undergo cyclic periods of growth (anagen), destruction (catagen) and rest (telogen). Matrix cells are thought to maintain their proliferative capacity through close association with dermal papilla during anagen. During catagen, withdrawal of growth signals results in massive apoptosis of the lower two thirds of the epidermal hair follicle. As a result, the dermal papilla is dragged through the dermis and comes to rest close to the permanent bulge region (telogen), during which the old hair shaft may be shed. At the onset of a new anagen phase, epidermal stem cells are stimulated to divide in response to signals from the dermal papilla. Epidermal progenitors proliferate to regenerate the matrix cells and their differentiated progeny necessary for a functional hair. Transient Shh signaling is required during the telogen-anagen transition and deregulated Hh responses can result in uncontrolled progenitor growth in BCC tumors. Key: ORS, outer root sheath; IRS, inner root sheath; IFE, interfollicular epidermis.
83 Recombination experiments suggested the first signal arising from the mesenchyme instructs regions of the pluripotent ectoderm to elongate into regularly spaced placode structures. 84 Epidermal signals from the placode cue underlying mesenchymal fibroblasts to organize into dermal condensates, or dermal prepapilla. A second “dermal message” from the condensate subsequently prompts epidermal cells in the placode to proliferate and grow down into the dermis, forming a hair peg, which will eventually engulf the dermal condensate to form a dermal papilla. This close epidermal-mesenchymal crosstalk is believed to stimulate further proliferation and differentiation of epidermal cells into many components of the mature hair follicle. 83 In the hair peg, epidermal cells that lose contact with the dermal papilla become outer root sheath (ORS) cells, a compartment that is contiguous with the basal layer of the interfollicular epidermis (IFE). 85 Matrix cells are highly proliferative epidermal cells that maintain contact with the dermal papilla and start to adopt distinct differentiation programs on withdrawal from the cell cycle. These differentiating cells move upwards in morphologically distinct concentric cylinders of cells that emerge at staggered intervals during postnatal development; the outer three cylinders of the inner root sheath (IRS) develop first, while the three central hair shaft layers arise later. 84 The final epidermal lineage to emerge is the oil-rich sebocytes, which populate the sebaceous glands, off the upper portion of hair follicles.
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=eurekah.section.62117
