Secretogranin-Ⅱ plays a critical role in zebrafish neurovascular modeling

• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2018,（5）
• 页码范围: 388-401
• 页数: 14页
• 语种: 英文
• DOI: 10.1093/jmcb/mjy027

摘要

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 sgllo and sgllb.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.