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.