Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development

Yingdi Wang, Nicolas Baeyens, Federico Corti, Keiichiro Tanaka, Jennifer S. Fang, Jiasheng Zhang, Yu Jin, Brian Coon, Karen K. Hirschi, Martin A. Schwartz, Michael Simons

Research output: Contribution to journalArticle

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Abstract

The role of fluid shear stress in vasculature development and remodeling is well appreciated. However, the mechanisms regulating these effects remain elusive. We show that abnormal flow sensing in lymphatic endothelial cells (LECs) caused by Sdc4 or Pecam1 deletion in mice results in impaired lymphatic vessel remodeling, including abnormal valve morphogenesis. Ablation of either gene leads to the formation of irregular, enlarged and excessively branched lymphatic vessels. In both cases, lymphatic valve-forming endothelial cells are randomly oriented, resulting in the formation of abnormal valves. These abnormalities are much more pronounced in Sdc4−/−; Pecam1−/− double-knockout mice, which develop severe edema. In vitro, SDC4 knockdown human LECs fail to align under flow and exhibit high expression of the planar cell polarity protein VANGL2. Reducing VANGL2 levels in SDC4 knockdown LECs restores their alignment under flow, while VANGL2 overexpression in wild-type LECs mimics the flow alignment abnormalities seen in SDC4 knockdown LECs. SDC4 thus controls flow-induced LEC polarization via regulation of VANGL2 expression.

Original languageEnglish (US)
Pages (from-to)4441-4451
Number of pages11
JournalDevelopment (Cambridge)
Volume143
Issue number23
DOIs
StatePublished - Dec 1 2016

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Syndecan-4
Embryonic Development
Endothelial Cells
Lymphatic Vessels
Cell Polarity
Morphogenesis
Knockout Mice
Edema

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Cite this

Wang, Y., Baeyens, N., Corti, F., Tanaka, K., Fang, J. S., Zhang, J., ... Simons, M. (2016). Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development. Development (Cambridge), 143(23), 4441-4451. https://doi.org/10.1242/dev.140129

Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development. / Wang, Yingdi; Baeyens, Nicolas; Corti, Federico; Tanaka, Keiichiro; Fang, Jennifer S.; Zhang, Jiasheng; Jin, Yu; Coon, Brian; Hirschi, Karen K.; Schwartz, Martin A.; Simons, Michael.

In: Development (Cambridge), Vol. 143, No. 23, 01.12.2016, p. 4441-4451.

Research output: Contribution to journalArticle

Wang, Y, Baeyens, N, Corti, F, Tanaka, K, Fang, JS, Zhang, J, Jin, Y, Coon, B, Hirschi, KK, Schwartz, MA & Simons, M 2016, 'Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development', Development (Cambridge), vol. 143, no. 23, pp. 4441-4451. https://doi.org/10.1242/dev.140129
Wang Y, Baeyens N, Corti F, Tanaka K, Fang JS, Zhang J et al. Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development. Development (Cambridge). 2016 Dec 1;143(23):4441-4451. https://doi.org/10.1242/dev.140129
Wang, Yingdi ; Baeyens, Nicolas ; Corti, Federico ; Tanaka, Keiichiro ; Fang, Jennifer S. ; Zhang, Jiasheng ; Jin, Yu ; Coon, Brian ; Hirschi, Karen K. ; Schwartz, Martin A. ; Simons, Michael. / Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development. In: Development (Cambridge). 2016 ; Vol. 143, No. 23. pp. 4441-4451.
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