Secretogranln-II plays a critical role in zebrafis neurovascular modeling  

作　　者：Binbin Tao Hongling Hu Kimberly Mitchell Ji Chen Haibo Jia Zuoyan Zhu Vance L. Trudeau Wei Hu 

机构地区：[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

出　　处：《Journal of Molecular Cell Biology》2018年第5期388-401,共14页分子细胞生物学报（英文版）

摘　　要：Secretoneurin （SN） is a neuropeptide derived from specific proteolytic processing of the precursor secretogranin II （Sgll）. In zebrafish and other teleosts, there are two paralogs named sglla and sgllb. Our results showed that neurons expressing sgllb were aligned with central arteries in the hindbrain, demonstrating a close neurovascular association. Both sgllb-/- and sgllo-/-/sgllb-/- mutant embryos were defective in hindbrain central artery development due to impairment of migration and proliferation of central artery cells. Further study revealed that sgllb is non-ceU autonomous and required for central artery development. Hindbrain arterial and venous network identities were not affected in sgllb-/- 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 sgllb-/- mutant embryos. Reactivation of MAPK or PI3K/AKT in endothelial cells could partially rescue the central artery developmental defects in the sgllb mutants. This studV provides the first in vivo evidence that sgllb ptavs a critical rote in neurovascutar modeling of the hindbrain. Targeting the Sgll system may, therefore, represent a new avenue for the treatment of vascular defects in the central nervous system.

关 键 词：Secretogranin-II SECRETONEURIN TALENs NEUROVASCULAR zebrafish 

分 类 号：Q421[生物学—神经生物学] Q66[生物学—生理学]