PUBLICATION
The catalytic activity and secretion of zebrafish RNases are essential for their in vivo function in motor neurons and vasculature
- Authors
- Ferguson, R., Holloway, D.E., Chandrasekhar, A., Acharya, K.R., Subramanian, V.
- ID
- ZDB-PUB-190203-13
- Date
- 2019
- Source
- Scientific Reports 9: 1107 (Journal)
- Registered Authors
- Chandrasekhar, Anand
- Keywords
- none
- MeSH Terms
-
- Ribonuclease, Pancreatic/genetics
- Ribonuclease, Pancreatic/metabolism*
- Cell Movement
- Motor Neurons/metabolism*
- Motor Neurons/physiology
- PubMed
- 30710110 Full text @ Sci. Rep.
Abstract
Angiogenin (hANG), a member of the Ribonuclease A superfamily has angiogenic, neurotrophic and neuroprotective activities. Mutations in hANG have been found in patients with Amyotrophic lateral sclerosis (ALS). The zebrafish (Danio rerio) rnasel-1, 2 and 3 are orthologues of hANG and of these only Rnasel-1 and Rnasel-2 have been shown to be angiogenic. Herein we show that NCI-65828, a potent and specific small molecule inhibitor of hANG inhibits Rnasel-1 to a similar extent. Treatment of early zebrafish embryos with NCI-65828, or with terrein, a fungal metabolite which prevents the secretion of hANG, resulted in spinal neuron aberrations as well defects in trunk vasculature. Our detailed expression analysis and inhibitor studies suggest that Rnasel-1 plays important roles in neuronal migration and pathfinding as well as in angiogenesis in zebrafish. Our studies suggest the usefulness of the zebrafish as a model to dissect the molecular consequences of the ANG ALS variants.
Genes / Markers
Figure Gallery (5 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping