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Secretogranin-II plays a critical role in zebrafish neurovascular modeling Free
Binbin Tao 1,2, Hongling Hu 1,2, Kimberly Mitchell 3, Ji Chen 1, Haibo Jia 4, Zuoyan Zhu 1, Vance L. Trudeau 3,* , and Wei Hu 1,*
1 State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
2 University of the Chinese Academy of Sciences, Beijing 10049, China
3 Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada
4 Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, HuaZhong University of Science and Technology,
Wuhan 430074, China
*Correspondence to:Wei Hu, E-mail: huwei@ihb.ac.cn; Vance L. Trudeau, E-mail: trudeauv@uottawa.ca
J Mol Cell Biol, Volume 10, Issue 5, October 2018, Pages 388-401  https://doi.org/10.1093/jmcb/mjy027
Keyword: Secretogranin-II, secretoneurin, TALENs, neurovascular, zebrafish

Secretoneurin (SN) is a neuropeptide derived from specific proteolytic processing of the precursor secretogranin II (SgII). In zebrafish and other teleosts, there are two paralogs named sgIIa and sgIIb. Our results showed that neurons expressing sgIIb were aligned with central arteries in the hindbrain, demonstrating a close neurovascular association. Both sgIIb−/− and sgIIa−/−/sgIIb−/− mutant embryos were defective in hindbrain central artery development due to impairment of migration and proliferation of central artery cells. Further study revealed that sgIIb is non-cell autonomous and required for central artery development. Hindbrain arterial and venous network identities were not affected in sgIIb−/− mutant embryos, and the mRNA levels of Notch and VEGF pathway-related genes were not altered. However, the activation of MAPK and PI3K/AKT pathways was inhibited in sgIIb−/− mutant embryos. Reactivation of MAPK or PI3K/AKT in endothelial cells could partially rescue the central artery developmental defects in the sgIIb mutants. This study provides the first in vivo evidence that sgIIb plays a critical role in neurovascular modeling of the hindbrain. Targeting the SgII system may, therefore, represent a new avenue for the treatment of vascular defects in the central nervous system.