TY - JOUR
T1 - Multiple mouse models of primary lymphedema exhibit distinct defects in lymphovenous valve development
AU - Geng, Xin
AU - Cha, Boksik
AU - Mahamud, Md Riaj
AU - Lim, Kim Chew
AU - Silasi-Mansat, Robert
AU - Uddin, Mohammad K.M.
AU - Miura, Naoyuki
AU - Xia, Lijun
AU - Simon, Alexander M.
AU - Engel, James Douglas
AU - Chen, Hong
AU - Lupu, Florea
AU - Srinivasan, R. Sathish
N1 - Publisher Copyright:
© 2015 The Authors.
PY - 2016
Y1 - 2016
N2 - 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, LVV-forming endothelial cells (LVV-ECs) differentiate from PROX1+ progenitors and delaminate from the luminal side of the veins. Second, LVV-ECs aggregate, align perpendicular to the direction of lymph flow and establish lympho-venous connections. Finally, LVVs mature with the recruitment of mural cells. LVV morphogenesis is disrupted in four different mouse models of primary lymphedema and the severity of LVV defects correlate with that of lymphedema. In summary, we have provided the first and the most comprehensive analysis of LVV development. Furthermore, our work suggests that aberrant LVVs contribute to lymphedema.
AB - 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, LVV-forming endothelial cells (LVV-ECs) differentiate from PROX1+ progenitors and delaminate from the luminal side of the veins. Second, LVV-ECs aggregate, align perpendicular to the direction of lymph flow and establish lympho-venous connections. Finally, LVVs mature with the recruitment of mural cells. LVV morphogenesis is disrupted in four different mouse models of primary lymphedema and the severity of LVV defects correlate with that of lymphedema. In summary, we have provided the first and the most comprehensive analysis of LVV development. Furthermore, our work suggests that aberrant LVVs contribute to lymphedema.
UR - http://www.scopus.com/inward/record.url?scp=84958566099&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84958566099&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2015.10.022
DO - 10.1016/j.ydbio.2015.10.022
M3 - Article
C2 - 26542011
AN - SCOPUS:84958566099
SN - 0012-1606
VL - 409
SP - 218
EP - 233
JO - Developmental biology
JF - Developmental biology
IS - 1
ER -