Recently, the presence of lymphatics has been demonstrated and characterized in the dura mater, which is in contrast to the well-accepted view indicating the lack of a classical lymphatic drainage system of the central nervous system (CNS). Moreover, the role of meningeal lymphatics in the pathogenesis of Alzheimer's disease and multiple sclerosis was suggested. However, the possible regulators of the developmental program and function of meningeal lymphatics remain unclear. Here, we aimed at characterizing the lymph flow dependence of the developmental program and function of the meningeal lymphatics. First, we demonstrated that lymphatics present in the dura mater are involved in the uptake and transport of macromolecules from the CNS. Meningeal lymphatics develop during the postnatal period which process involves the maturation of the vessels. The formation of mature meningeal lymphatics coincides with the increase of the drainage of macromolecules from the CNS to the deep cervical lymph nodes. Importantly, the structural remodeling and maturation of meningeal lymphatics is impaired in Plcγ2 -/- mice with reduced lymph flow. Furthermore, macromolecule uptake and transport by the meningeal lymphatics are also affected in Plcγ2 -/- mice. Collectively, lymph flow-induced mechanical forces are required for the postnatal formation of mature and functional meningeal lymphatic vessels. Defining lymph flow-dependence of the development and function of meningeal lymphatics may lead to better understanding of the pathogenesis of neurological diseases including Alzheimer's disease and multiple sclerosis.

中文翻译：

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淋巴流诱导成熟和功能性脑膜淋巴管的产后形成。

最近，在硬脑膜中已经证明并鉴定了淋巴管的存在，这与公认的观点相反，即缺乏经典的中枢神经系统淋巴引流系统。此外，提示脑膜淋巴管在阿尔茨海默氏病和多发性硬化症的发病机理中的作用。但是，尚不清楚脑膜淋巴管发育程序和功能的可能调节因子。在这里，我们旨在表征淋巴液对脑膜淋巴管发育程序和功能的依赖性。首先，我们证明了硬脑膜中存在的淋巴管细胞参与了从中枢神经系统吸收和转运大分子。脑膜淋巴管在出生后发育，其过程涉及血管的成熟。成熟的脑膜淋巴管的形成与大分子从中枢神经系统向颈深淋巴结的排泄增加相吻合。重要的是，在淋巴流量减少的Plcγ2-/-小鼠中，脑膜淋巴管的结构重塑和成熟受到损害。此外，在Plcγ2-/-小鼠中，脑膜淋巴管对大分子的摄取和运输也受到影响。总的来说，淋巴流诱导的机械力是出生后形成功能正常的脑膜淋巴管所必需的。定义淋巴流量对脑膜淋巴管发育和功能的依赖性可能有助于更好地了解神经系统疾病（包括阿尔茨海默氏病）的发病机理