Chinese, Canadian Scientists Uncover Novel Functions of Neuroendocrine Factor SN in Neurovascular Development

Recently, researchers from Institute of Hydrobiology (IHB) of Chinese Academy of Sciences, cooperating with Prof. Vance L. Trudeau’s team from University of Ottawa, used transcription activator-like effector nucleases (TALENs) to generate zebrafish sgIIa-/-, sgIIb-/-, sgIIa-/-/sgIIb-/- mutant lines, and revealed that sgIIb plays a critical role in neurovascular modeling in the hindbrain. The study was published in Journal of Molecular Cell Biology as a cover story.

The neuropeptide secretoneurin (SN) is a short 31-43 conserved peptide derived from the SgII (Secretogranin II) precursor protein by prohormone convertase-mediated processing. Various physiological roles have been assigned to SN, including those related to reproduction, neuroinflammation and neurotransmitter release. Until now, the function of the SN (or SgII) in the development of vertebrates was unknown.

In this study, researchers provided extensive anatomical evidence for their conclusions, including a video-recording of the formation of cerebral vasculature in the living zebrafish larva.

They confirmed that sgIIb-/- mutant embryos were defective in hindbrain central artery development due to impairment of migration and proliferation of central artery cells, while neuronal cells were not affected in hindbrain of sgIIb-/- mutant embryos.

Further study demonstrated sgIIb is non cell–autonomous and required for central artery development. The role of sgIIb in neurovascular development is mediated by activation of the MAPK and PI3K/AKT pathways in vivo.

The findings bring new insight into molecular mechanisms of angiogenesis, and suggest a potential gene target for neurovascular therapy.

Angiogenesis is a critical process during animal development for the maintenance of tissue growth and organ function.

This work was supported by the National Natural Science Foundation of China, Natural Sciences and Engineering Research Council of Canada, and the University of Ottawa International Research Acceleration Program.


Time-lapse confocal 3D imaging of the CtA development in sgIIb–/–;Tg(kdrl:EGFP) zebrafish embryos (right), compared with Tg(kdrl:EGFP) embryos (left) during 36-45 hours post-fertilization. The scale bar represents 100um. (Video by IHB) 


Cover of the journal