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

Research output: Contribution to journalArticle

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.

LanguageEnglish
Pages1107
JournalScientific Reports
Volume9
Issue number1
DOIs
StatusPublished - 1 Feb 2019

Cite this

The catalytic activity and secretion of zebrafish RNases are essential for their in vivo function in motor neurons and vasculature. / Ferguson, Ross; Holloway, Daniel E; Chandrasekhar, Anand; Acharya, K Ravi; Subramanian, Vasanta.

In: Scientific Reports, Vol. 9, No. 1, 01.02.2019, p. 1107.

Research output: Contribution to journalArticle

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