Distinct mechanisms underlie pattern formation in the skin and skin appendages

Abstract

SummaryPatterns form with the break of homogeneity, leading to the emergence of new structure or arrangement. There are different physiological and pathological mechanisms which lead to the formation of patterns. Here we first introduce the basics of pattern formation and their possible biological basis. We then discuss different categories of skin patterns and their potential underlying molecular mechanisms. Some patterns, such as the lines of Blaschko and naevus, are based on cell lineage and genetic mosaicism. Other patterns, such as regional specific skin appendages, can be set by distinct combinatorial molecular codes, which in turn may be set by morphogenetic gradients. There are also some patterns, such as the arrangement of hair follicles (hair whorls) and fingerprints, which involve genetics as well as stochastic epigenetic events based on physical-chemical principles. Many appendage primordia are laid out in developmental waves. In the adult, some patterns, such as those involving cycling hair follicles, may appear as traveling waves in mutant mice. Since skin appendages can renew themselves in regeneration, their size and shape can still change in the adult via regulation by hormones and the environment. Some lesion patterns are based on pathological changes involving the above processes and can be used as diagnostic criteria in medicine. Understanding the different mechanisms which lead to patterns on the skin will help us appreciate their full significance in morphogenesis and medical research. Much remains to be learned about complex pattern formation, a level between molecular biology and organism phenotypes.

Linkage and Segregation Analysis of Black and Brindle Coat Color in Domestic Dogs

“…However, the allelic system for tabby striping is probably opposite to brindle: the presence of black tabby stripes (t b ) is recessive to the absence of such stripes associated with the Abyssinian (T a ) allele in cats, while the presence of black brindle stripes (k br ) is dominant to the absence of such stripes associated with the yellow (k y ) allele in dogs. Equally important, the pattern of tabby striping is alternating and regular, consistent with an underlying pattern based on a Turing-like reaction-diffusion mechanism (Suzuki et al 2003;Jiang et al 2004;Widelitz et al 2006). By contrast, the pattern of brindle stripes is irregular and variegated, most consistent with an epigenetic mechanism (discussed further below).…”

“…The brindle-stripe pattern is similar to Blaschko lines in humans, thought to be caused by mosaicism of gene expression in keratinocyte clones (Bolognia et al 1994;Widelitz et al 2006). From this perspective, the fascinating pattern caused by the k br mutation is most likely explained by an unstable allele-between yellow (k y ) and black (K B )-that acquires one or the other state by chance and then maintains that state epigenetically as keratinocytes divide and migrate during embryonic development.…”

“…Brindle stripes form an irregular pattern, typically with a ''V'' shape over the dorsum and an ''S'' shape over flanks and ventrum and are somewhat reminiscent of a dermatologic phenomenon in humans known as lines of Blaschko, thought to be caused by mosaicism of gene expression in keratinocyte clones ( Jackson 1976;Bolognia et al 1994;Widelitz et al 2006). Brindle segregates as a single gene in a variety of dog breeds, such as the boxer, greyhound, and French bulldog, and has been thought by some authors to be caused by variation in Agouti, but by others to be caused by variation in Mc1r (Winge 1950;Little 1957;Willis 1989).…”

Tiers of Clonal Organization in the Epidermis: The Epidermal Proliferation Unit Revisited

“…One of the most striking examples of cutaneous mosaicism can be seen in the Lines of Blaschko [6]. These lines are regional segments (many centimeters across) of human skin, consistent among individuals, which lie horizontal to the anterior-posterior axis but do not correspond exactly to dermatomes or the metameric structure of vertebrates.…”

Partial differential equations for self-organization in cellular and developmental biology

“…For their time, they were adequate in that the prevailing biological data were also at the macroscopic coarse-grained level. In fact, they can still be considered to be very useful paradigm models for patterning on the macroscopic scale, either alone or coupled together [22,60,97,98].…”