Secretogranin-II Plays A Critical Role In Zebrafish Neurovascular Modeling

Summary statementNeurons 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.\n\nAbstractSecretoneurin (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.