Postnatal development of lymphatic vasculature in the brain meninges

• Published in: Developmental dynamics 2018-05, Vol.247 (5), p.741-753
• Main Authors: Izen, Rebecca M., Yamazaki, Tomoko, Nishinaka‐Arai, Yoko, Hong, Young‐Kwon, Mukouyama, Yoh‐Suke
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Bacterial artificial chromosomes; Blood vessels; Brain; Brain - blood supply; Central nervous system; dura mater; Embryos; Lymphatic system; lymphatic vessels; Lymphatic Vessels - embryology; meningeal lymphatics; Meninges; Meninges - embryology; Mice; Mice, Transgenic; Neuroimaging; Olfactory bulb; Prox1; Sinuses; Skin; Skin - embryology; Skull; Superior sagittal sinus
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.24624

Background: Traditionally, the central nervous system (CNS) has been viewed as an immune‐privileged environment with no lymphatic vessels. This view was partially overturned by the discovery of lymphatic vessels in the dural membrane that surrounds the brain, in contact with the interior surface of the skull. We here examine the distribution and developmental timing of these lymphatic vessels. Results: Using the Prox1‐GFP BAC transgenic reporter and immunostaining with antibodies to lymphatic markers LYVE‐1, Prox1, and Podoplanin, we have carried out whole‐mount imaging of dural lymphatic vasculature at postnatal stages. We have found that between birth and postnatal day (P) 13, lymphatic vessels extend alongside dural blood vessels from the side of the skull toward the midline. Between P13 and P20, lymphatic vessels along the transverse sinuses reach the superior sagittal sinus (SSS) and extend along the SSS toward the olfactory bulb. Conclusions: Compared with the embryonic developmental timing of lymphatic vessels in other tissues, e.g. skin, dural lymphatic vessel development is dramatically delayed. This study provides useful anatomical data for continuing investigations of the fundamental mechanisms that underlie dural lymphatic vessel development. Developmental Dynamics 247:741–753, 2018. © 2018 Wiley Periodicals, Inc. Key Findings Lymphatic vessels, Meningeal lymphatics, Prox1, Dura mater.