The lymphatic system maintains tissue fluid balance, and dysfunction of lymphatic vessels and valves causes human lymphedema syndromes. Yet, our knowledge of the molecular mechanisms underlying lymphatic vessel development is still limited. Here, we show that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of lymphatic vessel development. Endothelial-specific Cdk5 knockdown causes congenital lymphatic dysfunction and lymphedema due to defective lymphatic vessel patterning and valve formation. We identify the transcription factor Foxc2 as a key substrate of Cdk5 in the lymphatic vasculature, mechanistically linking Cdk5 to lymphatic development and valve morphogenesis. Collectively, our findings show that Cdk5-Foxc2 interaction represents a critical regulator of lymphatic vessel development and the transcriptional network underlying lymphatic vascular remodeling.

中文翻译：

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Cdk5通过Foxc2的磷酸化控制淋巴管的发育和功能。

淋巴系统维持组织液平衡，淋巴管和瓣膜功能障碍导致人淋巴水肿综合征。但是，我们对淋巴管发育的分子机制的认识仍然有限。在这里，我们显示出细胞周期蛋白依赖性激酶5（Cdk5）是淋巴管发育的重要调节剂。内皮细胞特异性Cdk5敲低会由于先天性淋巴管构图和瓣膜形成而导致先天性淋巴功能障碍和淋巴水肿。我们确定转录因子Foxc2作为Cdk5在淋巴管系统中的关键底物，将Cdk5机械连接到淋巴管的发育和瓣膜的形态发生。总的来说，