The morphological effects of mutation and disease are often critical to our understanding of normal and abnormal function. The power and popularity of zebrafish as a forward and reverse genetic vertebrate model system, combined with its small size, have made it an ideal model in which to study the genetics of histologically scorable phenotypes. The presence of multiple tissue types in this organism's small larvae also makes it a potentially important model for toxicological analysis. Studying histological phenotypes is greatly enhanced by high-throughput methods of histology. Here, we describe details of high-throughput histology of the zebrafish using larval arrays, along with recent advances in mold design and discussion of work in progress that will lead to easier ways for people in the field to more rapidly score phenotypes in arrays. These detailed descriptions, together with the troubleshooting guide, should enable any laboratory with ties to a histology facility to perform high-throughput histology of zebrafish.
Bibliographical noteFunding Information:
We thank Peggy Hubley for fish facility maintenance, Melissa Lighty for graphics assistance, Jing Fu and the Department of Industrial and Manufacturing Engineering for mold construction, and Fred Dee (U. Iowa) and the staff of Aperio Corp for their advice with scanning. This work was supported by National Institutes of Health Grants 5R01HD040179 and 5R24RR017441, the Life Sciences Greenhouse of Central Pennsylvania, and The Pennsylvania Tobacco Settlement Fund to K.C. Images were taken in the Penn State Zebrafish Functional Genomics Core Facility.
- Array genetic screen
- Atlas screen
- High-throughput toxicology method