Multiple mouse models of primary lymphedema exhibit distinct defects in lymphovenous valve development

作者：Geng Xin; Cha Boksik; Mahamud Md Riaj; Lim Kim Chew; Silasi Mansat Robert; Uddin Mohammad K M; Miura Naoyuki; Xia Lijun; Simon Alexander M; Engel James Douglas; Chen Hong; Lupu Florea; Srinivasan R Sathish^*

来源：Developmental Biology, 2016, 409(1): 218-233.

DOI：10.1016/j.ydbio.2015.10.022

Lymph is returned to the blood circulation exclusively via four lymphovenous valves (LVVs). Despite their vital importance, the architecture and development of LVVs is poorly understood. We analyzed the formation of LVVs at the molecular and ultrastructural levels during mouse embryogenesis and identified three critical steps. First, LW-forming endothelial cells (LW-ECs) differentiate from PROX1(+) progenitors and delaminate from the luminal side of the veins. Second, LW-ECs aggregate, align perpendicular to the direction of lymph flow and establish lympho-venous connections. Finally, LVVs mature with the recruitment of mural cells. LW morphogenesis is disrupted in four different mouse models of primary lymphedema and the severity of LW defects correlate with that of lymphedema. In summary, we have provided the first and the most comprehensive analysis of LW development. Furthermore, our work suggests that aberrant LVVs contribute to lymphedema.

• 出版日期2016-1-1