Rete ridges form via evolutionarily distinct mechanisms in mammalian skin
Article Date: 04 February 2026
Article URL: https://www.nature.com/articles/s41586-025-10055-5
Article Image: https://media.springernature.com/lw685/springer-static/image/art%3A10.1038%2Fs41586-025-10055-5/MediaObjects/41586_2025_10055_Fig1_HTML.png
Summary
This study maps how epidermal rete ridges — the undulating basal epidermal structures that support a thicker, functionally complex skin — form in mammals and shows they arise by mechanisms distinct from other epidermal appendages (hair follicles, sweat glands, fingerprint ridges). Using comparative histology across mammals, single-cell and spatial transcriptomics in pig and reanalysis of human datasets, plus genetic perturbations in mouse and pig models, the authors find that:
– Rete ridges form perinatally in humans and pigs, with pig development closely mirroring human timing (major formation around birth and the first postnatal week). Dermal “pockets” beneath inter-ridge epidermis vascularise as ridges mature.
– Species bearing rete ridges generally have thicker epidermis and lower hair density; species without rete ridges (many rodents, some primates) have thinner epidermis.
– Rete ridge formation is transcriptionally and mechanistically distinct from placode-driven appendages: it does not require LEF1–WNT or EDA–EDAR signalling.
– Instead, postnatal activation of epidermal BMP signalling (BMP2/7, SMAD1/5 and BMPR receptors) and NOTCH ligands (JAG1, DLL1) accompanies rete ridge initiation and maturation; epidermal BMP activity is necessary for ridge formation in mouse fingerpads and for rete maturation.
– The epidermis and underlying dermal pocket form an active signalling niche (FGF, PDGF, VEGF/ANGPTL pathways among others) that recruits fibroblasts and vasculature, supporting epidermal thickening and maintenance.
Key Points
- Rete ridges appear perinatally in humans and pigs and primarily form postnatally in pigs during the first week of life.
- Mammals with rete ridges have markedly thicker epidermis; rete ridges appear essential to create and maintain that thickness.
- Rete ridges do not form via LEF1–WNT or EDA–EDAR placode programmes used by hair follicles, sweat glands and fingerprint ridges.
- Postnatal epidermal BMP signalling (BMP2/BMP7 → SMAD1/5 → BMPR) is activated during rete ridge formation and is required for their development (loss or antagonism of BMP blocks ridge formation).
- Dermal “pockets” beneath ridges are vascularised niches; epidermal–dermal signalling (PDGF, VEGF, ANGPTL, FGF, TGFβ, EGF) drives recruitment and maturation of dermal cells, supporting epidermal expansion.
- Mouse volar fingerpads act as a conserved model for rete ridge formation and were used to show functional BMP dependence (K14-Noggin and Bmpr1a loss-of-function impair ridges).
- Altering hair density genetically (e.g. epidermal Lef1 knockout) does not automatically induce rete ridges — hair density and rete ridge formation are uncoupled processes.
- Datasets (scRNA-seq and stereo-seq) and interactive resources are provided to the community for further study.
Why should I read this?
Quick and dirty: if you care about skin — whether for developmental biology, wound healing, ageing or regenerative medicine — this paper tells you that rete ridges are NOT just a by-product of other appendage programmes. They’re a separate, postnatal, BMP-driven architecture with its own epidermal–dermal niche. The authors read the data so you don’t have to: big comparative histology, single-cell + spatial transcriptomics, genetics in mice and pigs, and wound/regeneration tests — all pointing to BMP as the switch. Handy if you’re thinking about scar repair, graft design or modelling human skin.
Author takeaway (punchy)
Rete ridges are their own thing. They form late, they need BMP, and they give non-furry skin its bulk and resilience. This changes how we think about restoring human-like skin structure after injury or in ageing: target the rete-ridge niche and its BMP signalling if you want a thicker, better-connected epidermis.
Context and relevance
This work reframes epidermal appendage biology by separating the developmental programmes that produce placode-derived structures (hair, sweat glands, volar ridges) from the postnatal programme that builds rete ridges. It is relevant to several ongoing trends:
– Regenerative medicine: informing strategies to rebuild epidermal architecture after burns or in chronic wounds.
– Ageing and dermatology: rete ridge loss or dermal pocket alteration links to age-related thinning and disease; understanding drivers could improve interventions.
– Evolutionary and comparative biology: shows how convergent skin adaptations (thicker epidermis in less-furred species) arise through recruitment of distinct signalling networks rather than simple loss/gain of hair programmes.
The study is timely because it combines comparative anatomy with modern single-cell and spatial technologies and functional genetics — providing a path from mechanism to potential therapeutic targets.