The embryogenesis of hair follicles

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Hair follicle embryogenesis

Hair follicle appendage formation is the result of a complex sequence of signals between the dermal mesenchyme and the overlying epithelium. Although, the precise initiating stimulus is yet to be identified, morphologically, induction, organogenesis and cytodifferentiation phases can be determined. The hair follicle formation events can be divided into at least eight distinct developmental stages. These stages are similar in rodents and humans and probably all mammals.

The development of human hair follicles first starts back in the gestational stage - between the 8th and 12th week to be particular. The dermal signalling elements are present in forms of gradients over the developing fetus. Probably in response to these dermal elements the first placodes are formed out of the primitive epithelium. The placode induces the aggregation of underlying dermal cells to mesenchymal condensates; and that leads to the first visible stage in hair follicle development. The very first hair follicle placodes grow in the eyebrow, upper lip and chin regions. Placode formation subsequently expands in a wave back and down over the skin of the fetus. With the dermal instructions to the cells, their associated overlying ectodermal placodes start to proliferate and initiate penetration of the dermis; stage 2 of development.

After that the epithelial cells start a downward growth extending into the skin dermis. In this process, the dermal condensate cells lead the way. The hair follicles grow angularly into the dermis - the degree of angle is determined by the location of the hair follicle. The initial placode formation stage is followed by an early peg stage (stage 3) hair follicle. When the fetus reaches 12 to 14 of weeks gestation, the epithelial base of the hair pegs on the scalp invaginate to envelop the dermal cell condensates forming dermal papillae. This stage of development is described as the bulbous hair peg stage or stage 4 in development.

The 13 to 16 weeks gestation sees stage 5 of hair follicle formation. During this stage, the superficial portions of the hair follicles subsequently develop two distinct, asymmetrical bulges of cells on the “posterior” side of the follicle. It forms an obtuse angle to the skin surface. The upper bulge closest to the skin surface, eventually forms the sebaceous gland while the lower bulge forms the location of the presumptive follicular stem cells. These will anchor in future the developing arrector pili muscle to the hair follicle. The arrector pili muscle, which is usually first seen in the dermis near the developing sebaceous gland, itself develops independently of the hair follicle. The arrector pili muscle keeps on growing downwards to connect to the bulge region - all the while the follicle pushes deeper into the dermis. It can be noted that the arrector pili muscle does not develop in hair follicles that by now start growing perpendicular to the skin. The example of such growth can be seen in eyelash hair follicles, follicles of the external auditory canal, and those of the nasal orifice.

The outer cells of the bulge develop into sebaceous gland and proliferate. Some of them however differentiate into lipogenic cells that progressively accumulate lipid. Maternal hormones cause sebaceous gland hypertrophy and temporarily increase synthesis and secretion of sebum during the second and third trimesters. At the time of birth, the release of the sebaceous glands from the influence of maternal hormones, become relatively quiescent until endogenous hormone production increases in puberty. In humans, some hair follicles will develop a third superficial bulge of cells above the cells destined to become the sebaceous gland. This third bulge of cells leads to the formation of an apocrine gland. The face and scalp are the most common locations, in human bodies that experience hair follicle associated aprocrine gland development. This hair follicle associated formation of apocrine glands are common in all mammalian species, in humans the association is relatively infrequent.

In the second trimester, the hair follicles start differentiating and ultimately form the seven layers of cells in concentric cylinders seen in mature hair follicles. A core of epithelial cells that begin near the bulb at the end of stage 4 or early stage 5, separates from the peripheral epithelial cells which later become the outer root sheath, continuous with the non-folliclular epithelium. The epithelial cell core, resting on the top of the dermal papilla, further differentiates into the inner root sheath Henle, Huxley, and cuticle layers, and the central core of matrix cells that proliferate and give rise to the hair fiber cuticle, cortex, and later in terminal hairs, the medulla. Stage 6 is marked by the noticeable development and growth of the hair fiber. At this stage, the hair fiber and its inner root sheath elongate, and the peripheral epithelial cells move aside to allow the cone of the central core of cells to move upwards away from the bulb. By the time, fetus enters into 19-21 weeks gestation, the hair follicles development also reaches stage 7 when the hair canals form. By stage 8 the formation of hair follicles are complete and the initial hair fibers erupt from the skin. The initial lanugo hair of the first anagen hair growth phase starts from 24-28 weeks of gestation.

Hair follicle embryogenesis diagram
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