Anagen can be divided into six stages. During early phases, hair progenitor cells proliferate, envelope the growing dermal papilla, grow downwards into the skin and begin to differentiate into the hair shaft and inner root sheath. In mid anagen, melanocytes located in the hair matrix show pigment-producing activity, and the newly formed hair shaft begins to develop. In late anagen, full restoration of the hair fibre-producing unit is achieved, which is characterised by the formation of the epithelial hair bulb surrounding the dermal papilla, located deep in the subcutaneous tissue, and the new hair shaft emerges from the skin surface [59,63,64]. During anagen, active signal exchanges occur between the epithelial cells of the hair bulb and the fibroblasts of the dermal papilla. Actively proliferating and postmitotic keratinocytes of the hair matrix express receptors and/or intracellular signalling components of a variety of signalling pathways (^-catenin/Lef-1, c-kit, c-met, FGFR2, IGF-IR), while the corresponding ligands are expressed in the dermal papilla (Wnt5a, SCF, HGF, FGF7, IGF-1) (reviewed in [54,63]).
In addition to hair follicle tissue remodelling, skin innervation and vascular networks also undergo substantial changes with the progression of the anagen stage [65,66]. Perifollicular vascularisation is significantly increased during anagen. It correlates with the upreg – ulation of the expression of vascular endothelial growth factor (VEGF) mRNA, a potent angiogenic growth factor, produced by keratinocytes of the outer root sheath. In transgenic mice overexpressing VEGF, perifollicular vascularisation was strongly induced, which resulted in accelerated hair growth and increased size of hair follicles and hair shafts [67]. In contrast, application of suppressors of angiogenesis leads to hair growth reduction [68]. Therefore, cutaneous vasculature may have a great impact on the hair shaft producing activity of hair follicle cells.