Danio rerio (zebrafish) are a powerful experimental model for genetic and developmental studies. Adaptation of zebrafish to study seizures was initially established using the common convulsant agent pentylenetetrazole (PTZ). Larval PTZ-exposed zebrafish exhibit clear behavioral convulsions and abnormal electrographic activity, reminiscent of interictal and ictal epileptiform discharge. By using this model, our laboratory developed simple locomotion-based and electrophysiological assays to monitor and quantify seizures in larval zebrafish. Zebrafish also offer multiple advantages for rapid genetic manipulation and high-throughput phenotype-based drug screening. Combining these seizure assays with genetically modified zebrafish that represent Dravet syndrome, a rare genetic epilepsy, ultimately contributed to a phenotype-based screen of over 3500 drugs. Several drugs identified in these zebrafish screens are currently in clinical or compassionate-use trials. The emergence of this 'aquarium-to-bedside' approach suggests that broader efforts to adapt and improve upon this zebrafish-centric strategy can drive a variety of exciting new discoveries.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277967 | PMC |
| http://dx.doi.org/10.1242/dmm.049080 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The mammalian kidney develops in three sequential stages referred to as the pronephros, mesonephros, and metanephros, each developing from the preceding form. All three phases of kidney development utilize epithelized tubules called nephrons, which function to take in filtrate from the blood or coelom and selectively reabsorb solutes the organism needs, leaving waste products to be excreted as urine. The pronephros are heavily studied in aquatic organisms such as zebrafish and Xenopus, as they develop quickly and are functional.
View Article and Find Full Text PDFThe retinal pigment epithelium (RPE) surrounds the posterior eye and maintains the health and function of the photoreceptors. Consequently, RPE dysfunction or damage has a devastating impact on vision. Due to complex etiologies, there are currently no cures for patients with RPE degenerative diseases, which remain some of the most prevalent causes of vision loss worldwide.
View Article and Find Full Text PDFUnlabelled: During vertebrate development, the heart primarily arises from mesoderm, with crucial contributions from cardiac neural crest cells that migrate to the heart and form a variety of cardiovascular derivatives. Here, by integrating bulk and single cell RNA-seq with ATAC-seq, we identify a gene regulatory subcircuit specific to migratory cardiac crest cells composed of key transcription factors and . Notably, we show that cells expressing the canonical neural crest gene are essential for proper cardiac regeneration in adult zebrafish.
View Article and Find Full Text PDFCerebrovascular endothelial cell (EC) subtypes characterized by blood-brain barrier (BBB) properties or fenestrated pores are essential components of brain-blood interfaces, supporting brain function and homeostasis. To date, the origins and developmental mechanisms underlying this heterogeneous EC network remain largely unclear. Using single-cell-resolution lineage tracing in zebrafish, we discover a multipotent vascular niche at embryonic capillary borders that generates ECs with BBB or fenestrated molecular identity.
View Article and Find Full Text PDFZebrafish models of genetic epilepsy benefit from the ability to assess disease-relevant knock-out alleles with numerous tools, including genetically encoded calcium indicators (GECIs) and hypopigmentation alleles to improve visualization. However, there may be unintended effects of these manipulations on the phenotypes under investigation. There is also debate regarding the use of stable loss-of-function (LoF) alleles in zebrafish, due to genetic compensation (GC).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!