Cyclic renewal in three ectodermal appendage follicles: Hairs, feathers and teeth.

Ectodermal appendages display a range of renewal mechanisms, with some undergoing continuous growth and others experiencing cyclic regeneration. The latter requires sustainable epithelial stem cells and mesenchymal niche essential for interacting with these stem cells. Furthermore, certain appendages dynamically adjust their mesenchymal niche in response to environmental factors, such as hormonal fluctuations, sex, and seasonal changes, enabling them to cyclically renew with different appendages phenotypes to adapt to different environments and to different life stages. Here we focus on amniotes, including reptiles, birds, and mammals, which exhibit integumentary adaptations that enable their survival across various ecological environments, from aquatic habitats and terrestrial landscapes to aerial domains. We highlight three representative integument appendage follicles: teeth, feathers, and hairs. Despite independent evolutionary origins, these structures share a fundamental architectural design characterized by the presence of stem cells and mesenchymal niches. They differ in the spatial arrangement and topology of these components. By examining the distinct architectural features of these follicles, we demonstrate the different strategies they use to orchestrate the physiological regenerative cycling, from growth initiation to cessation and molting, and regeneration after wounding. We delve into known molecular controls that govern these processes and unravel the evolutionary insights. We also identify new cell interactions that underlie the emergence of evolutionary novel follicle components. Various amniote scales have evolved independently with different configurations, but all lack follicle architecture and maintain homeostasis using a strategy similar to that of skin. The convergently evolved follicles in hairs, feathers, and teeth utilize different designs to achieve cyclic renewability, allowing them to produce spatially and temporally specific appendage phenotypes, thus enhancing the adaptability of the integumentary interface to external environmental pressures. This, in turn, enriches our understanding of evolutionary developmental biology (Evo-Devo) of the integument, shedding light on the intricate interplay between form and function across diverse taxa.