Fig. 3: CSF drainage through periorbital, nasal and hard palate lymphatics to the submandibular lymph node.

a, Sequence of intracisternal infusion of 1.0 μl TMR–dextran or FluoSpheres over 1 min into Prox1–GFP mice with analysis at 60 min. b,c, Fluorescence images of TMR–dextran (red) in head and neck lymphatics after removal of facial skin. The TMR–dextran signal is strong in scLV-1, scLV-2 and the periorbital region (red arrowhead). The white dashed line box marks the region enlarged in panel c. Scale bar, 1 mm. Representative of n = 4 mice from three independent experiments. d, Drawing showing the CSF drainage route from meningeal lymphatics near the orbit to the submandibular lymph node. e, Immunofluorescence images of FluoSpheres in periorbital (yellow arrowhead) and orbital fissure (white arrowhead) lymphatics. The white dashed lines indicate the lymphatic pathway from the orbital fissure. The orange dashed line marks the intracranial–extracranial boundary. The red dashed line boxes mark regions enlarged in panels showing that FluoSpheres (red) are abundant in periorbital (panel 1) and orbital fissure (panel 2) lymphatics (red arrowheads). Scale bar, 1 mm. Representative of n = 4 mice from three independent experiments. f, Immunofluorescence images of FluoSpheres in nasal lymphatics at 60 min after intracisternal infusion. In the nasal mucosa, FluoSpheres (red) are abundant in lymphatics (green arrowheads) but not in venous sinusoids (red arrowheads; also PROX1⁺). The white boxes in panel f are enlarged in panels 3–5. The white asterisk in panel f marks the junction of the nasal mucosa and hard palate. Scale bar, 500 µm. Representative of n = 5 mice from three independent experiments. g, Fluorescence image showing TMR–dextran (red) in nasal sidewall lymphatics (blue arrowhead), hard palate (orange arrowhead), and scLV-1 and scLV-2 (green arrowheads). Scale bar, 1 mm. Representative of n = 4 mice from three independent experiments. Anatomical positions are indicated in the top right corner.