Background: The compromise of blood brain barrier (BBB) integrity is often
associated with human hemorrhage stroke and neurodegeneration diseases, including
retina diseases, such as age-related macular degeneration and diabetic retinopathy.
Brain pericytes play pivotal roles in regulation and maintenance of BBB integrity.
However, the mechanisms underlying brain pericyte development to establish BBB
integrity remain unclear.
Methods: Zebrafish transgenic lines Tg(flk1:GFP; gata1:dsRed), Tg(flk1:GFP),
Tg(fli1:GFP) and Tg(BRE:GFP) were used in this work. The functional studies of bmp3
were performed by mopholino oligonucleotide (MO) injection, dye-based permeability
assay, RT-PCR, in vivo imaging, immunofluorescence staining and statics analysis.
Results: Here we report that bmp3 regulates BBB integrity in zebrafish brain by
promoting pericyte development. Knockdown of bmp3 with injection of bmp3-MO causes
intracerebral hemorrhage in zebrafish embryos. Meanwhile, disruption of bmp3 function
by bmp3-MO injection impairs cerebral pericyte coverage in zebrafish embryos.
Mechanistically, knockdown of bmp3 disrupts the pattern and activities of BMP signaling
in zebrafish brain, thus probably disrupting the balance of TGFβ/BMP signaling in
Conclusion: In summary, our data shows that bmp3 regulates BBB integrity potentially
by promoting pericyte development.