A Critical Review of Zebrafish Neurological Disease Models−1. The Premise: Neuroanatomical, Cellular and Genetic Homology and Experimental Tractability

Author:

Burgess Harold A1ORCID,Burton Edward A234ORCID

Affiliation:

1. Eunice Kennedy Shriver National Institute of Child Health and Human Development Division of Developmental Biology, , Bethesda, MD, 20892, USA

2. University of Pittsburgh Pittsburgh Institute for Neurodegenerative Diseases, , Pittsburgh, PA, 15260, USA

3. University of Pittsburgh Department of Neurology, , Pittsburgh, PA,15260, USA

4. Geriatric Research, Education, and Clinical Center, Pittsburgh VA Healthcare System , Pittsburgh, PA, 15240, USA

Abstract

AbstractThe last decade has seen a dramatic rise in the number of genes linked to neurological disorders, necessitating new models to explore underlying mechanisms and to test potential therapies. Over a similar period, many laboratories adopted zebrafish as a tractable model for studying brain development, defining neural circuits and performing chemical screens. Here we discuss strengths and limitations of using the zebrafish system to model neurological disorders. The underlying premise for many disease models is the high degree of homology between human and zebrafish genes, coupled with the conserved vertebrate Bauplan and repertoire of neurochemical signaling molecules. Yet, we caution that important evolutionary divergences often limit the extent to which human symptoms can be modeled meaningfully in zebrafish. We outline advances in genetic technologies that allow human mutations to be reproduced faithfully in zebrafish. Together with methods that visualize the development and function of neuronal pathways at the single cell level, there is now an unprecedented opportunity to understand how disease-associated genetic changes disrupt neural circuits, a level of analysis that is ideally suited to uncovering pathogenic changes in human brain disorders.

Funder

National Institute for Child Health and Human Development

NINDS

NIEHS

United States Department of Veterans Affairs

CurePSP

Pittsburgh Foundation

University of Pittsburgh

Publisher

Oxford University Press (OUP)

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Modeling Tauopathies in Zebrafish (Danio rerio);Journal of Evolutionary Biochemistry and Physiology;2023-11

2. Using Zebrafish in Preclinical Drug Studies: Challenges and Opportunities;Safety and Risk of Pharmacotherapy;2023-09-26

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