PUBLICATION
Secretogranin-II plays a critical role in zebrafish neurovascular modeling
- Authors
- Tao, B., Hu, H., Mitchell, K., Chen, J., Jia, H., Zhu, Z., Trudeau, V.L., Hu, W.
- ID
- ZDB-PUB-180515-9
- Date
- 2018
- Source
- Journal of molecular cell biology 10(5): 388-401 (Journal)
- Registered Authors
- Hu, Wei, Jia, Haibo, Trudeau, V.L., Zhu, Zuoyan
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Arteries/cytology
- Arteries/embryology*
- Cell Movement
- Cell Proliferation
- Embryo, Nonmammalian
- Extracellular Signal-Regulated MAP Kinases/metabolism
- Mutation
- Neurons/metabolism
- Phosphatidylinositol 3-Kinases/metabolism
- Proto-Oncogene Proteins c-akt/metabolism
- Receptors, Notch/metabolism
- Rhombencephalon/blood supply*
- Rhombencephalon/embryology
- Secretogranin II/genetics
- Secretogranin II/metabolism*
- Transcription Activator-Like Effector Nucleases
- Vascular Endothelial Growth Factor A/metabolism
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 29757409 Full text @ J. Mol. Cell Biol.
Citation
Tao, B., Hu, H., Mitchell, K., Chen, J., Jia, H., Zhu, Z., Trudeau, V.L., Hu, W. (2018) Secretogranin-II plays a critical role in zebrafish neurovascular modeling. Journal of molecular cell biology. 10(5):388-401.
Abstract
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 sgIIa and sgIIb. 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 were 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping