Murine dorsal hair type is genetically determined by polymorphisms in candidate genes that influence BMP and WNT signalling

Abstract

Experimental Dermatology. 2020;29:450-461. wileyonlinelibrary.com/journal/exd | INTRODUC TI ONIn both humans and mice there are multiple distinct hair types, each of which differs in size and shape. Hair curl is generated largely by kinks in the hair follicle (HF) through which the hair grows. [1] In mice, pelage HF development involves reciprocal mesenchymal-epithelial interactions [2] and takes place during foetal and perinatal skin development in three consecutive waves, forming four dorsal hair types: guard, awl, auchene and zigzag. [3] The first wave starts at embryonic day 14.5 (E14.5) and forms primary (guard) hairs. The second wave initiated at E16.5 forms secondary (awl and auchene) hairs.The final wave starts at E18.5 forming tertiary (zigzag) hairs. [4] Guard hairs have distinctively long shafts and have a sensory function. [5] About 3% of pelage hairs are guard, ~16% awl, ~8% auchene and AbstractMouse dorsal coat hair types, guard, awl, auchene and zigzag, develop in three consecutive waves. To date, it is unclear if these hair types are determined genetically through expression of specific factors or can change based on their mesenchymal environment. We undertook a novel approach to this question by studying individual hair type in 67 Collaborative Cross (CC) mouse lines and found significant variation in the proportion of each type between strains. Variation in the proportion of zigzag, awl and auchene, but not guard hair, was largely due to germline genetic variation.We utilised this variation to map a quantitative trait locus (QTL) on chromosome 12 that appears to influence a decision point switch controlling the propensity for either second (awl and auchene) or third wave (zigzag) hairs to develop. This locus contains two strong candidates, Sostdc1 and Twist1, each of which carry several ENCODE regulatory variants, specific to the causal allele, that can influence gene expression, are expressed in the developing hair follicle, and have been previously reported to be involved in regulating human and murine hair behaviour, but not hair subtype determination. Both of these genes are likely to play a part in hair type determination via regulation of BMP and/or WNT signalling. K E Y W O R D S hair, mouse, papilla, QTL, zigzag Graeme J. Walker and Kiarash Khosrotehrani equally contributed as senior authors.| 451

Characterization of Growth Secondary Hair in Min Pig Activated by Follicle Stem Cell Stimulated by Wnt and BMP Signaling Pathway

“…After an in-depth study of the gene expression differences in the three pig breeds, this study found that some signal factors related to hair circulation can promote the proliferation of hair follicle stem cells and the growth of hair follicles [ 49 ]. During hair follicle development, the Wnt and BMP signaling pathways can stimulate hair follicle growth [ 50 ]. With genetics and chromatin landscaping, researchers have found that the McSCs, BMP, and WNT pathways are stimulated following WNT-mediated activation, thereby triggering the commitment of proliferative progeny [ 51 ].…”

“…Opinions differ regarding whether the hair growth pattern is controlled by a single molecule of Wnt and BMP from stem cells [ 50 , 54 ]. Our results are the first to show that Min pigs specifically activate the Wnt signaling molecule of the stem cell in their skin with hair growth.…”