FAM83G/Fam83g genetic variants affect canine and murine hair formation

Abstract

FAM83G/Fam83g genetic variants have been described in dogs, mice and recently also in humans. They are associated with palmoplantar keratoderma and altered hair or coat phenotype, reported as wooly phenotype in mice. FAM83G/Fam83g is an unexplored effector of temporally and spatially coordinated Wnt and BMP signalling which are key pathways in pre- and postnatal hair follicle morphogenesis and differentiation. The aim of this study was to unravel phenotypic consequences of FAM83G/Fam83g variants on hair coat formation in dogs and mice. Our results show differences in hair types and hair shaft structures in both species. Additionally, mice exhibit deregulated hair cycle progression which timely correlates with defective Wnt signalling (Axin2) and Bmp2/4 expression. These results affirm the involvement of FAM83G in hair morphogenesis, hair follicle differentiation and cycling.

Pathogenic FAM83G palmoplantar keratoderma mutations inhibit the PAWS1:CK1α association and attenuate Wnt signalling.

“…We also cannot rule out the contributions of other signalling pathways known to be active in skin, including, but not limited to, TGF-β/BMP, FGF, and YAP/TAZ 12, 35– 37 . Given that PAWS1 is highly expressed in the epidermal layer and inner root sheath of hair follicles 9, 38 , it may be that PAWS1 is required for tissue-specific regulation of CK1α activity and modulation of signalling responses in these compartments. Characterisation of PAWS1 function in animal models or skin organotypic cultures will hopefully provide more definitive evidence of this in the future.…”

New developments in hair research

“…Not least, one might be able to investigate whether injury conditioned human dermal stem cells would prove more trichogenic in this assay system, and/or whether bulge stem cells exposed to chemotherapy and radiotherapy injury are less effective . It may also be possible to use these techniques to test the consequences of genetic mutations in different cell types, and/or to evaluate whether extracellular factors can modify trichogeneicity …”

Understanding skin morphogenesis across developmental, regenerative and evolutionary levels

“…It builds upon the seminal morphological guide proposed two decades ago by Paus et al, and incorporates new molecular‐level knowledge from recent single‐cell RNA‐sequencing studies . The study by Wong's group reports on the role of GATA6 in regulating maintenance of the uppermost hair follicle compartment, while another study explores the role of FAM83G, a putative effector of WNT and BMP signalling pathways, in hair follicle morphogenesis, differentiation and regenerative cycling . Ezhkova's group comprehensively compared the embryonic origin and signalling aspects of Merkel cell specification in hairless paw vs haired dorsal skin and reports on the regional differences .…”

“…Powerful insights on morphogenesis can be learned from emerging model organisms, whose skin has distinct anatomical or physiological features. In this issue, several works show how research on African spiny mice, African striped mice, pigs and dogs can advance the understanding of skin morphogenesis and regeneration. Interestingly, the degree to which different mammalian species can activate wound‐induced neogenesis programs can vary substantially.…”