Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos

William P. Dunworth, Jose Cardona-Costa, Esra Cagavi Bozkulak, Jun Dae Kim, Stryder Meadows, Johanna C. Fischer, Yeqi Wang, Ondine Cleaver, Yibing Qyang, Elke A. Ober, Suk Won Jin

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Rationale: The emergence of lymphatic endothelial cells (LECs) seems to be highly regulated during development. Although several factors that promote the differentiation of LECs in embryonic development have been identified, those that negatively regulate this process are largely unknown. Objective: Our aim was to delineate the role of bone morphogenetic protein (BMP) 2 signaling in lymphatic development. Methods and results: BMP2 signaling negatively regulates the formation of LECs. Developing LECs lack any detectable BMP signaling activity in both zebrafish and mouse embryos, and excess BMP2 signaling in zebrafish embryos and mouse embryonic stem cell-derived embryoid bodies substantially decrease the emergence of LECs. Mechanistically, BMP2 signaling induces expression of miR-31 and miR-181a in a SMAD-dependent mechanism, which in turn results in attenuated expression of prospero homeobox protein 1 during development. Conclusions: Our data identify BMP2 as a key negative regulator for the emergence of the lymphatic lineage during vertebrate development.

Original languageEnglish (US)
Pages (from-to)56-66
Number of pages11
JournalCirculation research
Issue number1
StatePublished - Jan 3 2014


  • BMP2 protein
  • developmental biology
  • lymphatic vessels
  • microRNAs

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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