Prox1 in Mammalian Lymphangiogenesis

描述（由申请人提供）：在正常条件下，淋巴网络通过从细胞外间隙引流淋巴液来维持体液稳态，从肠道吸收脂质，并将白色血细胞和抗原呈递细胞转运至淋巴器官。在感染期间，淋巴管系统是免疫应答的主要途径，并且在癌症中，肿瘤细胞经由淋巴管系统迁移到淋巴结和远端器官。淋巴系统的功能障碍可导致先天性或遗传性疾病，例如水肿，这是一种由淋巴吸收失衡引起的毁容和致残疾病，通常以四肢肿胀为特征。更好地了解控制正常淋巴管系统发育的细胞和分子特征，应有助于我们了解导致炎症、自身免疫、癌症和肥胖的病理性淋巴状况，并改善原发性和继发性水肿的临床治疗。 公共卫生相关性：在过去的十年中，由于分子标记物和具有不同程度淋巴缺陷的动物模型的可用性，我们对控制淋巴管系统形成的基因和机制的理解已经大大提高。这些知识不仅帮助我们提高了对淋巴管相关病理状况的理解，还帮助我们重新评估了淋巴管系统在健康和疾病中的功能作用。因此，增加我们对发育性淋巴管生成的理解应该继续影响我们对病理性淋巴状况的理解。

DESCRIPTION (provided by applicant): Under normal conditions, the lymphatic network maintains fluid homeostasis by draining lymph fluid from extracellular spaces, absorbs lipids from the intestinal tract, and transports white blood cells and antigen- presenting cells to lymphoid organs. During infection, the lymphatic vasculature is the main route for the immune response, and in cancer, tumor cells migrate via the lymphatic vasculature to lymph nodes and distant organs. Malfunctions of the lymphatic system can lead to congenital or inherited disorders such as lymphedema, a disfiguring and disabling disorder that is caused by imbalance in lymph absorption and often characterized by swelling of the extremities. A better knowledge of the cellular and molecular features controlling normal lymphatic vasculature development should facilitate our understanding of pathologic lymphatic conditions that lead to inflammation, autoimmunity, cancer, and obesity and to improve the clinical treatment of primary and secondary forms of lymphedema. PUBLIC HEALTH RELEVANCE: Our understanding of the genes and mechanisms controlling the formation of the lymphatic vasculature has improved greatly during the last decade thanks to the availability of molecular markers and animal models with various degrees of lymphatic defects. This knowledge has helped us not only to improve our understanding of lymphatics-related pathologic conditions but also to re-evaluate the functional roles of the lymphatic vasculature in health and disease. Therefore, increasing our understanding of developmental lymphangiogenesis should keep impacting on our understanding of pathologic lymphatic conditions.