Rete ridges form via evolutionarily distinct mechanisms in mammalian skin
Year: 2026
Type: article
Abstract: The loss of fur during human evolution has long mystified scientists and the public 1–5 . 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 humans 1,6–9 . Examination of human and pig skin development has shown that rete ridges form through a mechanism independent from those of hair follicles 10,11 and sweat glands 3,4,12–15 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.
Source: Nature
Authors: Sean M. Thompson, Violet S. Yaple, Gabriella H. Searle, Quan M. Phan, Jasson Makkar, Xiangzheng Cheng, Ruiqi Liu, Anna Pulawska-Czub, Corin Yanke, Natalie M. Williams, Isabelle V. Busch, Tommy T. Duong, Matteo V. Corneto, Zachary S. Jordan, Debarun Roy, Adam B. Salmon, Ov D. Slayden, Brian P. Hermann, David A. Stoltz, Michael J. Welsh, Ian A. Glass, Krzysztof Kobielak, Qing Nie, Suoqin Jin, Heiko T. Jansen, Michela Ciccarelli, Maksim V. Plikus, Iwona M. Driskell, Ryan R. Driskell
Institutions: Washington State University, Wuhan University, University of California, Irvine, University of Warsaw, The University of Texas at San Antonio, The University of Texas at San Antonio Health Science Center, South Texas Veterans Health Care System, Oregon National Primate Research Center, Oregon Health & Science University, University of Iowa, Howard Hughes Medical Institute, University of Washington
Language: English
Topic: Hair Growth and Disorders
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W7127635630