Bone morphogenetic protein 9 (BMP9) controls lymphatic vessel maturation and valve formation.

Sandrine Levet, Delphine Ciais, Galina Merdzhanova, Christine Mallet, Teresa A. Zimmers, Se Jin Lee, Fabrice P. Navarro, Isabelle Texier, Jean Jacques Feige, Sabine Bailly, Daniel Vittet

Research output: Contribution to journalArticle

Abstract

Lymphatic vessels are critical for the maintenance of tissue fluid homeostasis and their dysfunction contributes to several human diseases. The activin receptor-like kinase 1 (ALK1) is a transforming growth factor-β family type 1 receptor that is expressed on both blood and lymphatic endothelial cells (LECs). Its high-affinity ligand, bone morphogenetic protein 9 (BMP9), has been shown to be critical for retinal angiogenesis. The aim of this work was to investigate whether BMP9 could play a role in lymphatic development. We found that Bmp9 deficiency in mice causes abnormal lymphatic development. Bmp9-knockout (KO) pups presented hyperplastic mesenteric collecting vessels that maintained LYVE-1 expression. In accordance with this result, we found that BMP9 inhibited LYVE-1 expression in LECs in an ALK1-dependent manner. Bmp9-KO pups also presented a significant reduction in the number and in the maturation of mesenteric lymphatic valves at embryonic day 18.5 and at postnatal days 0 and 4. Interestingly, the expression of several genes known to be involved in valve formation (Foxc2, Connexin37, EphrinB2, and Neuropilin1) was upregulated by BMP9 in LECS. Finally, we demonstrated that Bmp9-KO neonates and adult mice had decreased lymphatic draining efficiency. These data identify BMP9 as an important extracellular regulator in the maturation of the lymphatic vascular network affecting valve development and lymphatic vessel function.

Original languageEnglish (US)
Pages (from-to)598-607
Number of pages10
JournalBlood
Volume122
Issue number4
DOIs
StatePublished - Jul 25 2013

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Growth Differentiation Factor 2
Lymphatic Vessels
Activin Receptors
Endothelial cells
Endothelial Cells
Transforming Growth Factors
Blood Vessels
Homeostasis
Blood
Genes
Maintenance
Tissue
Ligands
Gene Expression
Fluids

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Levet, S., Ciais, D., Merdzhanova, G., Mallet, C., Zimmers, T. A., Lee, S. J., ... Vittet, D. (2013). Bone morphogenetic protein 9 (BMP9) controls lymphatic vessel maturation and valve formation. Blood, 122(4), 598-607. https://doi.org/10.1182/blood-2012-12-472142

Bone morphogenetic protein 9 (BMP9) controls lymphatic vessel maturation and valve formation. / Levet, Sandrine; Ciais, Delphine; Merdzhanova, Galina; Mallet, Christine; Zimmers, Teresa A.; Lee, Se Jin; Navarro, Fabrice P.; Texier, Isabelle; Feige, Jean Jacques; Bailly, Sabine; Vittet, Daniel.

In: Blood, Vol. 122, No. 4, 25.07.2013, p. 598-607.

Research output: Contribution to journalArticle

Levet, S, Ciais, D, Merdzhanova, G, Mallet, C, Zimmers, TA, Lee, SJ, Navarro, FP, Texier, I, Feige, JJ, Bailly, S & Vittet, D 2013, 'Bone morphogenetic protein 9 (BMP9) controls lymphatic vessel maturation and valve formation.', Blood, vol. 122, no. 4, pp. 598-607. https://doi.org/10.1182/blood-2012-12-472142
Levet S, Ciais D, Merdzhanova G, Mallet C, Zimmers TA, Lee SJ et al. Bone morphogenetic protein 9 (BMP9) controls lymphatic vessel maturation and valve formation. Blood. 2013 Jul 25;122(4):598-607. https://doi.org/10.1182/blood-2012-12-472142
Levet, Sandrine ; Ciais, Delphine ; Merdzhanova, Galina ; Mallet, Christine ; Zimmers, Teresa A. ; Lee, Se Jin ; Navarro, Fabrice P. ; Texier, Isabelle ; Feige, Jean Jacques ; Bailly, Sabine ; Vittet, Daniel. / Bone morphogenetic protein 9 (BMP9) controls lymphatic vessel maturation and valve formation. In: Blood. 2013 ; Vol. 122, No. 4. pp. 598-607.
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