RRC ID 54982
Author Gupta T, Marquart GD, Horstick EJ, Tabor KM, Pajevic S, Burgess HA.
Title Morphometric analysis and neuroanatomical mapping of the zebrafish brain.
Journal Methods
Abstract Large-scale genomic studies have recently identified genetic variants causative for major neurodevelopmental disorders, such as intellectual disability and autism. However, determining how underlying developmental processes are affected by these mutations remains a significant challenge in the field. Zebrafish is an established model system in developmental neurogenetics that may be useful in uncovering the mechanisms of these mutations. Here we describe the use of voxel-intensity, deformation field, and volume-based morphometric techniques for the systematic and unbiased analysis of gene knock-down and environmental exposure-induced phenotypes in zebrafish. We first present a computational method for brain segmentation based on transgene expression patterns to create a comprehensive neuroanatomical map. This map allowed us to disclose statistically significant changes in brain microstructure and composition in neurodevelopmental models. We demonstrate the effectiveness of morphometric techniques in measuring changes in the relative size of neuroanatomical subdivisions in atoh7 morphant larvae and in identifying phenotypes in larvae treated with valproic acid, a chemical demonstrated to increase the risk of autism in humans. These tools enable rigorous evaluation of the effects of gene mutations and environmental exposures on neural development, providing an entry point for cellular and molecular analysis of basic developmental processes as well as neurodevelopmental and neurodegenerative disorders.
Volume 150
Pages 49-62
Published 2018-11-1
DOI 10.1016/j.ymeth.2018.06.008
PII S1046-2023(18)30011-2
PMID 29936090
PMC PMC6296225
MeSH Animals Animals, Genetically Modified Autistic Disorder / chemically induced Autistic Disorder / genetics Behavior, Animal / drug effects Behavior, Animal / physiology Brain / anatomy & histology Brain / diagnostic imaging* Brain / drug effects Brain / physiology Brain Mapping / instrumentation Brain Mapping / methods* Computer Simulation DNA-Binding Proteins / genetics Disease Models, Animal Embryo, Nonmammalian Gene Knockdown Techniques Humans Intravital Microscopy / instrumentation Intravital Microscopy / methods* Microscopy, Confocal / instrumentation Microscopy, Confocal / methods Morpholinos / genetics Neurogenesis / drug effects Neurogenesis / physiology Valproic Acid / toxicity Zebrafish / anatomy & histology Zebrafish / physiology* Zebrafish Proteins / genetics
IF 3.782
Times Cited 5
Zebrafish Tg(huC:GVP) Tg(vglut2a:loxP-DsRed-loxP-GFP) Tg(CM-isl1:GFP) Tg(gad1b:|R|-GFP)