Development and plasticity of meningeal lymphatic vessels
| Autor: | Mart Saarma, Aleksanteri Aspelund, Salli Antila, Sinem Karaman, Dmitri Chilov, Jean-Leon Thomas, Zhilin Li, Shentong Fang, Harri Nurmi, Merja H. Voutilainen, Kari Alitalo, Tapani K. Koppinen, Thomas Mathivet, Anne Eichmann, Jun-Hee Park, Mikko Airavaara |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Central Nervous System Pathology Indoles Meningeal lymphatic vessels Vascular Endothelial Growth Factor C Vascular Endothelial Growth Factor D Mice Meninges Cerebrospinal fluid Sunitinib Immunology and Allergy Lymphangiogenesis Research Articles Cerebrospinal Fluid Dependovirus Microspheres Lymphatic Endothelium Lymphatic system medicine.anatomical_structure Spinal Cord Vascular endothelial growth factor C Signal Transduction medicine.medical_specialty government.form_of_government Myocytes Smooth Muscle Immunology Central nervous system News Biology Insights Article 03 medical and health sciences medicine Humans Animals Pyrroles Protein Kinase Inhibitors Injections Intraventricular Lymphatic Vessels Biological Transport Vascular Endothelial Growth Factor Receptor-3 Mice Inbred C57BL 030104 developmental biology Animals Newborn government Lymph Nodes Glymphatic System Gene Deletion |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| DOI: | 10.1084/jem.20170391 |
| Popis: | Antila et al. show that meningeal lymphatic vessels in mice develop postnatally. Interruption of VEGF-C/VEGFR3 signal transduction arrests their development. In adult mice, VEGFR3 deletion and VEGFR3 blockers, including a clinically available tyrosine kinase inhibitor, induce regression of meningeal lymphatic vessels. The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement in neuropathological processes, yet little is known about their development or maintenance. We show here that meningeal LVs develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system (CNS). VEGF-C, expressed mainly in vascular smooth muscle cells, and VEGFR3 in lymphatic endothelial cells were essential for their development, whereas VEGF-D deletion had no effect. Surprisingly, in adult mice, the LVs showed regression after VEGF-C or VEGFR3 deletion, administration of the tyrosine kinase inhibitor sunitinib, or expression of VEGF-C/D trap, which also compromised the lymphatic drainage function. Conversely, an excess of VEGF-C induced meningeal lymphangiogenesis. The plasticity and regenerative potential of meningeal LVs should allow manipulation of cerebrospinal fluid drainage and neuropathological processes in the CNS. |
| Databáze: | OpenAIRE |
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