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
-
- Amyotrophic Lateral Sclerosis/genetics*
- Animals
- Blood Vessels/metabolism*
- Blood Vessels/physiology
- Catalysis
- Cell Movement
- Humans
- Motor Neurons/metabolism*
- Motor Neurons/physiology
- Mutation/genetics
- Neurogenesis
- Neurons, Efferent/physiology*
- Ribonuclease, Pancreatic/genetics
- Ribonuclease, Pancreatic/metabolism*
- Ribonucleases/genetics
- Ribonucleases/metabolism*
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 30710110 Full text @ Sci. Rep.
Citation
Ferguson, R., Holloway, D.E., Chandrasekhar, A., Acharya, K.R., Subramanian, V. (2019) The catalytic activity and secretion of zebrafish RNases are essential for their in vivo function in motor neurons and vasculature. Scientific Reports. 9:1107.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping