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Rete ridges form through evolutionarily distinct mechanisms from other appendages during mammalian skin development [1]

ABSTRACT: The loss of fur during human evolution has long mystified scientists and the public. This loss coincides with the acquisition of epidermal rete ridges, whose developmental timing and molecular mechanisms are poorly understood despite their prominence in humans. Examination of human and pig skin development revealed that rete ridges form through an independent mechanism from hair follicles and sweat glands by establishing interconnecting epidermal invaginations. We documented rete ridge occurrence across Mammalia, including in grizzly bears and dolphins, and showed that neonatal pig wounds can regenerate them de novo. Multi-species spatiotemporal transcriptomics identified significant signaling interactions between epidermal and dermal cells during rete ridge morphogenesis, particularly through BMP. We also demonstrated that murine fingerpad skin forms rete ridges and functionally requires epidermal BMP signaling. Therefore, we propose that the evolution of rete ridges in mammalian skin involved replacement of the molecular program for periodic patterning and subsequent downgrowth of discrete appendages, such as hair follicles and sweat glands, coupled with broad activation of BMP to generate an interconnecting rete ridge network organized around vascularized dermal pockets. Understanding these mechanisms may allow for the development of therapeutic approaches to regenerate epidermal appendages lost during wounding or disease in humans.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE255125 | GEO | 2026/09/01

REPOSITORIES: GEO

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Rete ridges form via evolutionarily distinct mechanisms in mammalian skin

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