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Hair follicle morphogenesis and epidermal homeostasis in we/we wal/wal mice with postnatal alopecia

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Abstract

Mice with skin and hair follicle (HF) defects are common models of human skin disorders. A mutant strain with the we/we wal/wal genotype develops alopecia. We found the hair shaft structure in the pelage of mutant mice to have significant defects. Although these mice lose their hair at 21 days, a label-retaining cell population persists in HFs until at least day 54. Depilation-induced anagen was accomplished in we/we wal/wal mutants but the resulting hair shafts were short and extremely deformed. Serious abnormalities in epidermis stratification and HF morphogenesis exist in we/we wal/wal homozygous E18.5 embryos. There were significantly fewer HF primordia in this mutant compared with wild type. We discovered specific structures, identified as invalid placodes, positive for ectodysplasin A1 receptor, nuclear β-catenin, and LEF1, which failed to invaginate, produced a double basal-like layer of epidermal cells, and lacked cylindrical keratinocytes. Specification of dermal papillae (DP) was impaired, and the papillary dermis expressed alkaline phosphatase and LEF1. We also detected DP-like groups of intensively stained cells in the absence of visible signs of folliculogenesis in the epidermis. We showed differentiation disturbances in the mutant embryonic E18.5 epidermis and HFs: The cornified layer was absent, the width of the spinous layer was reduced, and HFs lacked LEF1-positive precortex cells. In this study, we used a very interesting and useful mouse model of alopecia. The presence of symptoms of skin disorders in we/we wal/wal murine embryos correlates with the postnatal skin phenotype. This correlation may help to evaluate reasons of alopecia.

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Authors and Affiliations

  1. Department of Regenerative Medicine, Pirogov Russian National Research Medical University, 1 Ostrovityanova, Moscow, 117997, Russian Federation

    Alexandra Rippa

  2. Laboratory of Cell Proliferation, N.K. Koltsov Institute of Developmental Biology, 26 Vavilov Str., Moscow, 119334, Russian Federation

    Vasily Terskikh, Andrey Vasiliev & Ekaterina Vorotelyak

  3. Epigenetic Department, N.I. Vavilov Institute of General Genetics, 3, Gubkina Str., Moscow, 119991, Russian Federation

    Anastasia Nesterova

  4. Department of Cell Biology and Histology, Biological Faculty, Lomonosov Moscow State University, 1 Leninskiye Gory, Moscow, 119234, Russian Federation

    Ekaterina Vorotelyak

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  1. Alexandra Rippa
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  2. Vasily Terskikh
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Correspondence to Ekaterina Vorotelyak.

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Rippa, A., Terskikh, V., Nesterova, A. et al. Hair follicle morphogenesis and epidermal homeostasis in we/we wal/wal mice with postnatal alopecia. Histochem Cell Biol 143, 481–496 (2015). https://doi.org/10.1007/s00418-014-1291-1

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