PUBLICATION

Loss of circadian rhythmicity in bdnf knockout zebrafish larvae

Authors
D'Agostino, Y., Frigato, E., Noviello, T.M.R., Toni, M., Frabetti, F., Cigliano, L., Ceccarelli, M., Sordino, P., Cerulo, L., Bertolucci, C., D'Aniello, S.
ID
ZDB-PUB-220330-3
Date
2022
Source
iScience   25: 104054 (Journal)
Registered Authors
Bertolucci, Cristiano, D'Aniello, Salvatore, Frabetti, Flavia, Frigato, Elena, Sordino, Paolo
Keywords
Behavioral neuroscience, Cellular neuroscience, Developmental neuroscience, Molecular neuroscience
MeSH Terms
none
PubMed
35345456 Full text @ iScience
Abstract
Brain-derived neurotrophic factor (BDNF) plays a pivotal role in neuronal growth and differentiation, neuronal plasticity, learning, and memory. Using CRISPR/Cas9 technology, we generated a vital Bdnf null mutant line in zebrafish and carried out its molecular and behavioral characterization. Although no defects are evident on a morphological inspection, 66% of coding genes and 37% of microRNAs turned out to be differentially expressed in bdnf-/- compared with wild type sibling embryos. We deeply investigated the circadian clock pathway and confirmed changes in the rhythmic expression of clock (arntl1a, clock1a and clock2) and clock-controlled (aanat2) genes. The modulatory role of Bdnf on the zebrafish circadian clock was then validated by behavioral tests highlighting the absence of circadian activity rhythms in bdnf-/- larvae. The circadian behavior was partially rescued by pharmacological treatment. The bdnf-/- zebrafish line presented here is the first valuable and stable vertebrate model for the study of BDNF-related neurodevelopmental diseases.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping