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

Xin Geng, Boksik Cha, Md Riaj Mahamud, Kim Chew Lim, Robert Silasi-Mansat, Mohammad K M Uddin, Naoyuki Miura, Lijun Xia, Alex Simon, James Douglas Engel, Hong Chen, Florea Lupu, R. Sathish Srinivasan

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)218-233
Number of pages16
JournalDevelopmental Biology
Volume409
Issue number1
DOIs
StatePublished - 2016

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Lymphedema
Lymph
Blood Circulation
Morphogenesis
Embryonic Development
Veins
Endothelial Cells

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Cite this

Geng, X., Cha, B., Mahamud, M. R., Lim, K. C., Silasi-Mansat, R., Uddin, M. K. M., ... Srinivasan, R. S. (2016). Multiple mouse models of primary lymphedema exhibit distinct defects in lymphovenous valve development. Developmental Biology, 409(1), 218-233. https://doi.org/10.1016/j.ydbio.2015.10.022

Multiple mouse models of primary lymphedema exhibit distinct defects in lymphovenous valve development. / Geng, Xin; Cha, Boksik; Mahamud, Md Riaj; Lim, Kim Chew; Silasi-Mansat, Robert; Uddin, Mohammad K M; Miura, Naoyuki; Xia, Lijun; Simon, Alex; Engel, James Douglas; Chen, Hong; Lupu, Florea; Srinivasan, R. Sathish.

In: Developmental Biology, Vol. 409, No. 1, 2016, p. 218-233.

Research output: Contribution to journalArticle

Geng, X, Cha, B, Mahamud, MR, Lim, KC, Silasi-Mansat, R, Uddin, MKM, Miura, N, Xia, L, Simon, A, Engel, JD, Chen, H, Lupu, F & Srinivasan, RS 2016, 'Multiple mouse models of primary lymphedema exhibit distinct defects in lymphovenous valve development', Developmental Biology, vol. 409, no. 1, pp. 218-233. https://doi.org/10.1016/j.ydbio.2015.10.022
Geng, Xin ; Cha, Boksik ; Mahamud, Md Riaj ; Lim, Kim Chew ; Silasi-Mansat, Robert ; Uddin, Mohammad K M ; Miura, Naoyuki ; Xia, Lijun ; Simon, Alex ; Engel, James Douglas ; Chen, Hong ; Lupu, Florea ; Srinivasan, R. Sathish. / Multiple mouse models of primary lymphedema exhibit distinct defects in lymphovenous valve development. In: Developmental Biology. 2016 ; Vol. 409, No. 1. pp. 218-233.
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