Journal article
Rete ridges form via evolutionarily distinct mechanisms in mammalian skin
Nature (London), Vol.651, pp.135-145
02/04/2026
DOI: 10.1038/s41586-025-10055-5
PMID: 41639458
Abstract
The loss of fur during human evolution has long mystified scientists and the public1, 2, 3, 4-5. Reduced hair density coincides with acquisition of epidermal rete ridges, the developmental timing and molecular mechanisms of which are poorly understood despite their prominence in humans1,6, 7, 8-9. Examination of human and pig skin development has shown that rete ridges form through a mechanism independent from those of hair follicles10,11 and sweat glands3,4,12, 13, 14-15 by establishing interconnected epidermal invaginations. Here we document the occurrence of rete ridges across Mammalia, including in grizzly bears and dolphins, and show that neonatal pig wounds can regenerate them de novo. Multispecies spatiotemporal transcriptomics identifies significant signalling interactions between epidermal and dermal cells during rete ridge morphogenesis, particularly through bone morphogenetic proteins (BMP). We also demonstrate that mouse fingerpad skin forms rete ridges and functionally requires epidermal BMP signalling. We propose that evolution of rete ridges in mammalian skin involved replacement of the molecular program for formation of discrete microscopic appendages, including hair follicles and sweat glands, with a distinct program for the interconnected appendage network. Broad epidermal activation of BMP is required for the development of rete ridge networks organized around underlying dermal pockets. Understanding rete ridge mechanisms may enable development of therapeutic approaches to regenerate epidermal appendages lost during wounding or disease in humans.
Details
- Title: Subtitle
- Rete ridges form via evolutionarily distinct mechanisms in mammalian skin
- Creators
- Sean M. Thompson - Washington State UniversityViolet S. Yaple - Washington State UniversityGabriella H. Searle - Washington State UniversityQuan M. Phan - Washington State UniversityJasson Makkar - Washington State UniversityXiangzheng Cheng - Wuhan UniversityRuiqi Liu - University of California, IrvineAnna Pulawska-Czub - University of WarsawCorin Yanke - Washington State UniversityNatalie M. Williams - Washington State UniversityIsabelle V. Busch - Washington State UniversityTommy T. Duong - Washington State UniversityMatteo V. Corneto - Washington State UniversityZachary S. Jordan - The University of Texas at San AntonioDebarun Roy - The University of Texas at San AntonioAdam B. Salmon - The University of Texas Health Science Center at San AntonioOv D. Slayden - Oregon National Primate Research CenterBrian P. Hermann - The University of Texas at San AntonioDavid A. Stoltz - University of IowaMichael J. Welsh - University of IowaIan A. Glass - University of WashingtonKrzysztof Kobielak - University of WarsawQing Nie - University of California, IrvineSuoqin Jin - Wuhan UniversityHeiko T. Jansen - Washington State UniversityMichela Ciccarelli - Washington State UniversityMaksim V. Plikus - University of California, IrvineIwona M. Driskell - Washington State UniversityRyan R. Driskell - Washington State UniversityUW Birth Defects Research Laboratory
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.651, pp.135-145
- DOI
- 10.1038/s41586-025-10055-5
- PMID
- 41639458
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Publisher
- NATURE PORTFOLIO
- Number of pages
- 27
- Grant note
- San Antonio Nathan Shock Center 5R24HD000836 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA T32GM008336 / NIH NIGMS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 101137006 / Horizon Europe POIR.04.04.00-00-4222/17-00 / Foundation for Polish Science (FNP) - European Union under the European Regional Development Fund 2022/45/B/NZ3/03811 / Opus Grant McIntire-Stennis project 1018967 / Interagency Grizzly Bear Committee, USDA NIFA 2015/19/B/NZ3/02948; 2019/33/B/NZ3/02966 / National Science Centre, Poland (NCN) Opus Grant AN-0000000062 / Chan Zuckerberg Initiative grant; Chan Zuckerberg Initiative (CZI) ONPRC
- Language
- English
- Date published
- 02/04/2026
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9985139302702771
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