Fig. 3: Rete ridge formation does not require LEF1–WNT or EDA–EDAR.
From: Rete ridges form via evolutionarily distinct mechanisms in mammalian skin
a, Rete ridges do not seem to form through LEF1+ placodes such as hair follicles and sweat glands. Representative immunostains for ITGA6 and LEF1 in E90 (n = 3), P0–3 (n = 3), P5 (n = 3), P10 (n = 2), 1 mo (n = 3) and 6 mo (n = 3) pig skin are shown. b, The epidermal placode transcriptional state is absent from postnatal skin that is forming rete ridges. Integration of E90, P3, P10 and 6 mo pig basal and dividing keratinocytes from scRNA-seq. Left, uniform manifold approximation and projection (UMAP) coloured by cluster. Middle, UMAP coloured by age. Right, bar plots representing the age contribution to each cluster and the overall age contribution to the integrated dataset. c, Rete ridge formation seems transcriptionally distinct from hair follicles, sweat glands and fingerprint ridges forming from epidermal placodes. Left, coexpression feature plots of the shared epidermal placode markers LEF1 and EDAR, the hair follicle (HF) markers WNT10B and SHH, the sweat gland (Sw) or volar fingerprint ridge (Fg) markers TGFA and SOX9, and WNT6 and LMX1A, and the postnatal rete ridge development and maturation markers BMP7 and BMP2, and JAG1 and DLL1. Expression of the left and right genes is indicated by red and green, respectively, and coexpression is indicated by yellow. The dashed navy polygon denotes the postnatal basal cell state associated with rete ridge formation and the green polygon the fetal basal bud/placode cell state labelled in b. Right, summary graphics of expression in fetal skin versus postnatal skin of marker genes associated with hair follicles, sweat glands, fingerprint ridges and rete ridges. d, Epidermal LEF1 is not required for rete ridge formation in mouse fingerpads. Left, representative immunostains of P21 mouse fingerpads from WT and Lef1-eKO mice stained for ITGA6 and KRT10 (n = 3). Right, quantification of fingerpad rete ridges per millimetre for WT (n = 3) and Lef1-eKO (eKO, n = 3) mouse fingerpads. P = 0.5075 from t-test. e, EDA signalling is not required for rete ridge formation and maturation in porcine skin. Left, schematic of EDA-KO pig generation42. Middle, representative H&E stains of P5 WT (n = 5) and EDA-KO (n = 5) pig skin and quantification of rete ridge density per millimetre. Each set represents five littermates. Right, representative H&E stains of age-matched 5 mo WT (n = 2) and EDA-KO (n = 2) pigs. P = 0.6555 from t-test. NS, not significant. Scale bars, 100 μm. Illustrations in a–d were created using BioRender. Thompson, S. (2026) https://BioRender.com/8rd8cz9.
