Mapping the molecular and structural specialization of the skin basement membrane for inter-tissue interactions

Inter-tissue interaction is fundamental to multicellularity. Although the basement membrane (BM) is located at tissue interfaces, its mode of action in inter-tissue interactions remains poorly understood, mainly because the molecular and structural details of the BM at distinct inter-tissue interfaces remain unclear. By combining quantitative transcriptomics and immunohistochemistry, we systematically identify the cellular origin, molecular identity and tissue distribution of extracellular matrix molecules in mouse hair follicles, and reveal that BM composition and architecture are exquisitely specialized for distinct inter-tissue interactions, including epidermal-fibroblast, epidermal-muscle and epidermal-nerve interactions. The epidermal-fibroblast interface, namely, hair germ-dermal papilla interface, makes asymmetrically organized side-specific heterogeneity in BM, defined by the newly characterized interface, hook and mesh BMs. One component of these BMs, laminin 5, is required for the topological and functional integrity of hair germ-dermal papilla interactions. Our study highlights the significance of BM heterogeneity in distinct inter-tissue interactions.