Bone Morphogenetic Protein 2 Signaling Negatively Modulates Lymphatic Development in Vertebrate Embryos
Rationale: The emergence of lymphatic endothelial cells (LECs) appears to be highly regulated during development. While several factors that promote the differentiation of LECs in embryonic development have been identified, those that negatively regulate this process are largely unknown.
Objective: To delineate the role of BMP2 signaling on 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 (ES) cell-derived embryoid bodies (EBs) 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, result attenuated expression of PROX1 during development.
Conclusions: Our data identify BMP2 as a key negative regulator for the emergence of the lymphatic lineage during vertebrate development.
- vertebrate development
- developmental biology
- lymphatic capillary
- signaling pathways
- Received August 20, 2013.
- Revision received October 8, 2013.
- Accepted October 11, 2013.