To grow or not to grow: hair morphogenesis and human genetic hair disorders

Abstract

Mouse models have greatly helped in elucidating the molecular mechanisms involved in hair formation and regeneration. Recent publications have reviewed the genes involved in mouse hair development based on the phenotype of transgenic, knockout and mutant animal models. While much of this information has been instrumental in determining molecular aspects of human hair development and cycling, mice exhibit a specific pattern of hair morphogenesis and hair distribution throughout the body that cannot be directly correlated to human hair. In this mini-review, we discuss specific aspects of human hair follicle development and present an up-to-date summary of human genetic disorders associated with abnormalities in hair follicle morphogenesis, structure or regeneration.

Keywords: Alopecia; Genetic disorders; Hair follicle; Morphogenesis; Shaft differentiation.

Fig. 1

Hair morphogenesis, differentiation and structure. (A) Sections of fetal human hair follicles at placode, germ, peg and hair differentiation stages (between 80 and 170 days). (B) Full anagen human hair follicle at 126 day of development. (C) Left panel, Human lower hair follicle and bulb region depicting the different hair compartments. Right panel, Scanning electron microscopy image of terminal human hair shaft. HM, Hair matrix; SG, sebaceous gland; Bu, Bulge; DP, Dermal papilla; ORS, outer root sheath; IRS, inner root sheath. Images of human skin sections were kindly provided by Dr. Karen Holbrook.

Fig. 2

Desmosomes and human genetic hair disorders. Schematic representation of desmosome (A) and corneodesmosome (B) indicating components mutated in different human hair disorders. Panel C indicates mutations in factors (proteases and inhibitors) involved in desmosome degradation and associated hair disorders. mb, plasma membranes of cell 1 and cell 2.

Fig. 3

Keratins and human genetic hair disorders. Schematic representation of hair follicle indicating the compartment-specific keratin expression and mutations associated with different human hair disorders. DP, dermal papilla; ORS, outer root sheath; CL, companion layer; IRS, inner root sheath.