TY - JOUR T1 - Secretogranin-II plays a critical role in zebrafish neurovascular modeling JF - bioRxiv DO - 10.1101/123125 SP - 123125 AU - Binbin Tao AU - Hongling Hu AU - Kimberly Mitchell AU - Ji Chen AU - Haibo Jia AU - Zuoyan Zhu AU - Vance L. Trudeau AU - Wei Hu Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/01/123125.abstract N2 - Neurons expressing sgIIb align with central arteries in hindbrain. We show that sgIIb is critical for neurovascular modeling the larval zebrafish mediated by MAPK and PI3K/AKT signaling in vivo.Abstract Secretoneurin (SN) is a neuropeptide derived from specific proteolytic processing of the precursor secretogranin II (SgII). In zebrafish and other teleosts there are 2 paralogs we previously named sgIIa and sgIIb. Our results showed that neurons expressing sgIIb were aligned with central arteries in hindbrain, demonstrating a close neurovascular association. Both sgIIb-/- and sgIIa-/- /sgIIb-/- mutant embryos were defective in hindbrain central artery development, while artery development in sgIIa-/- mutant embryos was not affected. 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 were inhibited in sgIIb-/- mutant embryos. Injection of a synthetic SNb mRNA or delivery of the protein kinase activator N-arachidonoyl-L-serine 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 the hindbrain. ER -