Chapter 2 47 maintenance of primary hair follicle placodes.25 Results from studies using embryonic mouse skin explants show that Bmp molecules are able to inhibit placode growth. This is further demonstrated by the ablation of the gene encoding Bmp receptor 1A (Bmpr1a) in the surface epithelium, which causes the lack of external hair.26 The HS and hair follicle IRS fail to differentiate in Bmpr1a-deficient mice, although follicle numbers remain normal. Fgfs and Fgf receptors are expressed at early stages of follicle development and also appear to promote follicle formation.27 Ablation of the mouse gene encoding Fgf receptor 2-IIIb causes defective development of the skin and hair follicles.28 Noggin can neutralize the inhibitory activity of Bmp signaling. Mice lacking the expression of Noggin show significant retardation of hair follicle morphogenesis as well as delay in the hair follicle growth phase in postnatal skin.29 Sonic hedgehog (Shh) is a pivotal growth signal for DP maturation, and is essential for hair follicle morphogenesis.30-32 Signals to promote placode formation also vary significantly between the different hair types.33 Growth of primary guard hair follicles requires Eda-A1, its receptor Edar and their downstream effector, the transcription factor NF-ĸB. Stimulation of the Eda-A1/ Edar/NF-ĸB pathway increases the expression of Shh and cyclin D1, leading to placode growth.34 In contrast, secondary awl hair follicle development is independent of Eda-A1/Edar/NF-ĸB signaling, but requires the Bmp antagonist Noggin and the transcription factor Lef-1.35 Inductive signals for zigzag hair placodes remain unknown, but mice with suppressed NF-ĸB activity fail to develop zigzag hair placodes.36 The development of human hair follicles begins between the eighth to twelfth week of gestation when primitive epithelium thickens in defined areas to form hair placodes under the stimulation of underlying condensates of mesenchymal cells.37 The formation of placodes expands cephalo-caudally in the fetus. In the subsequent “peg” stage when the fetus is in the twelfth to fourteenth week of gestation, the developing hair follicles show