Hair Development, Growth, and Loss 48 cell proliferation and downward extension of hair epithelium into the dermis and envelopment of the DC to form the DP. From the thirteenth to sixteenth week of gestation, the primordia of the sebaceous gland and the bulge, where the stem cells of epithelial cells and melanocytes reside, are developed. Epithelial cells in the hair follicles differentiate to form specific concentric rings, such as ORS and IRS, in the second trimester. Later, the hair canals form with emergence of HS from the skin surface in the nineteenth through twenty-first weeks of gestation. By the end of the second trimester, un-pigmented, fine, and un-medullated hairs, namely lanugo hairs, cover the whole fetus. In months eight and nine, the first hair cycle of lanugo hair ends with subsequent hair shedding and replacement by vellus hair on the trunk and terminal or vellus hair on the scalp. During the first year of life, the hairs on the scalp are still synchronized in growth and telogen hairs predominate. The vellus hair on the scalp, eyebrows and eyelashes is gradually replaced by thicker intermediate hair and then terminal hair as the hair cycle goes on after birth. At puberty, further transformation of vellus hair into terminal hair occurs at the pubic, axillary, and beard areas under the stimulation of androgens. Paradoxically, the effect of androgen may result in miniaturization of terminal hair into vellus- like hair on the scalp later in life.38 Hair Follicle Cycling Hair follicle morphogenesis proceeds throughout early postnatal life, which is often misinterpreted as “first anagen.” The follicle becomes fully mature as it elongates to reach the bottom of the dermis at around postnatal day 6 in mouse back skin.8 At this point, the DP then instructs the surrounding epithelial cells, referred to as matrix cells, to proliferate, move upward, and differentiate into the multiple epithelial structures that include the Henle, Huxley, and cuticle layers of the IRS, and the cuticle, cortex, and medulla layers of the HS. As cells terminally differentiate, they extrude their organelles and become tightly packed with keratin bundles.