The catalytic activity and secretion of zebrafish RNases are essential for their in vivo function in motor neurons and vasculature

Ross Ferguson, Daniel E Holloway, Anand Chandrasekhar, K Ravi Acharya, Vasanta Subramanian

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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.

Original languageEnglish
Article number1107
Pages (from-to)1-15
Number of pages15
JournalScientific Reports
Issue number1
Publication statusPublished - 1 Feb 2019

ASJC Scopus subject areas

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