Identification of lymphatic vessels in skull periosteum but not bone marrow reveals skull channel heterogeneity

Abstract

Whether and where lymphatic vessels occur in bone or bone marrow is unclear. The heterogeneity of skull channels and bone marrow remains poorly understood. Here, we used organ clearing, high-resolution three-dimensional imaging, cell type-specific mouse genetics, and surgical approaches to investigate skull vasculatures. We identified lymphatic vessels at the skull periosteum and found no evidence of lymphatic vessels in the cortical bones or skull bone marrow, where the lymphatic marker VEGFR3 labels blood vessels. Skull periosteum channels to the upper skin are found to occur more frequently in the parietal bone than the interparietal bone, whereas bone marrow is found more often in the interparietal bone than the parietal bone. Despite skull bone marrow expansion during aging, skull channels are significantly reduced, suggesting the aging-dependent uncoupling of skull channels and bone marrow. Together, our findings show lymphatic vessels are present in the skull periosteum but absent in bone marrow, with channel and bone marrow heterogeneity varying by skull region and age.