Morphogenesis, Growth Cycle and Molecular Regulation of Hair Follicles

Abstract

As one of the main appendages of skin, hair follicles play an important role in the process of skin regeneration. Hair follicle is a tiny organ formed by the interaction between epidermis and dermis, which has complex and fine structure and periodic growth characteristics. The hair growth cycle is divided into three continuous stages, growth (anagen), apoptosis-driven regression (catagen) and relative quiescence (telogen). And The Morphogenesis and cycle of hair follicles are regulated by a variety of signal pathways. When the signal molecules in the pathways are abnormal, it will affect the development and cycle of hair follicles, which will lead to hair follicle-related diseases.This article will review the structure, development, cycle and molecular regulation of hair follicles, in order to provide new ideas for solving diseases and forming functional hair follicle.

Keywords: BMP; WNT; hair cycling; hair follicles; morphogenesis.

FIGURE 1

Structure of hair follicle. (A) A human scalp hair follicle (anagen VI): the permanent (infundibulum, isthmus) and anagen associated (suprabulbar and bulbar area) components of the hair follicle. (B) Schematic diagram of the concentric layers of the hair follicle bulb, including hair shaft, IRS, outer root sheath, and connective tissue sheath. IRS, inner root sheath.

FIGURE 2

Morphogenesis and timing of hair follicle during mouse embryonic development. The most important developmental stages of mouse pelage hair follicles are divided into induction, organogenesis and cytodifferentiation.

FIGURE 3

The growth cycle of hair. (A) The time-scale for the hair cycle in female C57BL/6 mice during the first 14 weeks after birth (the upper part); The time-scale for the hair cycle in humans (the lower part). (B) The morphology of hair follicles at different stages of the hair cycle. Anagen: growth phase, catagen: regression phase, telogen: resting phase.

FIGURE 4

The molecular regulation of hair follicle morphogenesis and cycling. (A) WNT signaling path mode diagram. Schematic drawing illustrating canonical WNT signaling pathway mainly includes WNT protein, cell surface Frizzled receptor family, Dishevelled (DSH) receptor family protein, β-catenin, and axin/GSK-3/APC complex. β-catenin plays a key role in the canonical WNT signaling pathway. (B) BMP signaling pathway mode diagram. The classical BMP signaling pathway is that ligand BMP binds to phosphorylated serine and threonine receptors and is transported into cytoplasm. In cytoplasm, BMP combines with Smad1/5/8 and phosphorylates the C terminal of Smad1/5/8. The phosphorylated Smad1/5/8 combines with Smad4 and transports to the nucleus. (C) EDAR signaling path mode diagram. EDAR signaling pathway is mainly composed of EDA ligand, transmembrane receptor EDAR (including EDAA1 and EDAA2 subtypes), and intracellular binding protein EDARARR. (D) SHH signaling path mode diagram. Ptch binds to Smo to inhibit Smo activity. In the presence of Hh, the binding of Ptch1 to Hh protein eliminates the inhibitory effect on Smo, and Smo transmits signals to downstream Gli transcription factors through a complex transduction process.