103of the hair follicle is observed only in the case of deer antlers (Randall et al. 1993 ;
Thornton et al. 1996 ; Polykandriotis et al. 2010 ). The germinative epithelial cells in
the proximal region of the hair matrix are described as transit-amplifying cells
because they only survive through anagen (Reynolds and Jahoda 1991 and 1996 ).
At the end of anagen, cell division in the germinative hair matrix supplies the hair
differentiation of the hair shaft and the slowly developing IRS, and consequently the
hair follicle enters catagen (Stenn and Paus 2001 ; Millar 2002 ). During catagen, the
entire variable region is reduced to an epithelial column to form a secondary hair
germ, mainly by apoptosis of matrix, IRS and ORS epithelial cells, while bulge hair
follicle stem cells evade apoptosis (Millar 2002 ). Following catagen, the hair folli-
cles enter a telogen phase, which is acknowledged as a relatively quiescent and
resting phase (Stenn and Paus 2001 ; Millar 2002 ; Schneider et al. 2009 ).
The initiation of a new anagen phase in the adult hair cycle and embryonic fol-
liculogenesis are appreciated for sharing many features that are considered, at least
in part, to be different phenomena (Stenn and Paus 2001 ; Botchkarevn and
Kishimoto 2003 ; Schneider et al. 2009 ). The processes are distinguished as follows:
one is the organogenesis of a whole hair organ, and the other is the partial reproduc-
tion of a variable region of adult hair follicle (Botchkarevn and Kishimoto 2003 ;
Stenn et al. 2007 ). Both processes are characterized by the induction and control of
cell proliferation and differentiation to construct the hair-producing system and
maintain hair growth through epithelial-mesenchymal interactions, which are medi-
ated by similar signaling molecules (Botchkarevn and Kishimoto 2003 ). During
early anagen, the secondary hair germ forms a hair bulb, which grows progressively
downward and away from the bulge region (Botchkarevn and Kishimoto 2003 ).
Although the ORS cells of the bulge region readopt a quiescent, undifferentiated
epithelial cell phenotype in the lower portion of the hair matrix, the proliferative
potential is maintained through active Wnt signaling from dermal papilla cells and
consequent stabilization of β-catenin in matrix epithelial cells throughout anagen
(Stenn and Paus 2001 ; Botchkarevn and Kishimoto 2003 ; Schneider et al. 2009 ). In
the upper part of the hair matrix, proliferation is arrested and terminal differentia-
tion is initiated (Botchkarevn and Kishimoto 2003 ). Many pioneering investigations
have revealed multiple molecules that regulate hair lineages, such as Wnt/b-catenin/
Lef1, Notch1/Jagged/Delta, BMPs/BMPR1a, Msx and Foxn1 for hair shaft devel-
opment and IGF1 and HGF production, and VEGF for the maintenance of anagen
(Botchkarevn and Kishimoto 2003 ; Schneider et al. 2009 ; Lim and Nusse 2013 ).
The anagen-catagen transition, which is associated with a remarkable decrease in
the exchange of epithelial-mesenchymal interaction signals in anagen, determines
the hair length of the corresponding hair types (Randall et al. 1993 ; Hibberts et al.
1998 ). Several studies suggest that this transition timing is controlled by an internal
biological clock because ectopically transplanted hair follicles can retain their own
inherent hair cycling (39). During catagen, the lower part of the hair follicle rapidly
regresses via apoptosis of epithelial cells as a consequence of the increased expres-
sion of apoptosis stimulation factors, such as FGF5, TGFβ, TNFα, and neurotrophin
(Stenn and Paus 2001 ; Botchkarevn and Kishimoto 2003 ; Wang et al. 2012 ). Upon
completion of catagen, the hair follicle enters telogen, which can be separated into
6 Functional Hair Follicle Regeneration