PUBLICATION
Embryonic spinocerebellar ataxia type 37 AUUUC repeat RNA causes neurodevelopmental defects in zebrafish
- Authors
- Castro, A.F., Figueiredo, A.S., Loureiro, J.R., Azevedo, M.M., Sampaio, P., Valentim, A.M., Bessa, J., Silveira, I.
- ID
- ZDB-PUB-260320-1
- Date
- 2026
- Source
- Disease models & mechanisms 19: dmm052636 (Journal)
- Registered Authors
- Bessa, Jose
- Keywords
- Axonal Outgrowth, Familial Adult Myoclonic Epilepsy (FAME), Intronic DAB1 ATTTC Repeat, NOVA2, Pentanucleotide Repeat Disease, Synaptic Innervation Defects
- MeSH Terms
- none
- PubMed
- 41854242 Full text @ Dis. Model. Mech.
Citation
Castro, A.F., Figueiredo, A.S., Loureiro, J.R., Azevedo, M.M., Sampaio, P., Valentim, A.M., Bessa, J., Silveira, I. (2026) Embryonic spinocerebellar ataxia type 37 AUUUC repeat RNA causes neurodevelopmental defects in zebrafish. Disease models & mechanisms. 19:dmm052636.
Abstract
Onset of many neurodegenerative and neuromuscular diseases usually starts in adulthood; however, recent advances point toward neurodevelopmental changes as drivers of late neurodegeneration. How early neuropathological features occur in these conditions remains unclear, which is critical for timely therapeutic intervention. Here, we provide evidence that neurodevelopmental axonal defects initiate a motor phenotype in a zebrafish model of spinocerebellar ataxia type 37 (SCA37), a degenerative hereditary condition caused by an ATTTC repeat in the DAB1 gene. We investigated neuronal defects triggered by the embryonic AUUUC repeat RNA and their effects later in life by transiently expressing this RNA in embryos and analyzing innervation and motor function. We found abnormalities in motor neuron axonal outgrowth and muscle innervation. We also discovered disrupted embryonic motor activity and reduced locomotor distance and velocity in late adult zebrafish, demonstrating motor impairment. Moreover, we showed that NOVA2 expression rescues axonal defects, indicating dysfunction of NOVA2-regulated neurodevelopmental processes. Overall, our results establish embryonic expression of the AUUUC repeat RNA as a driver of axonal and synaptic abnormalities, interfering with neuronal circuits and culminating in adult motor dysfunction.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping