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Skeletal muscle performs an essential function in human physiology with defects in genes encoding a variety of cellular components resulting in various types of inherited muscle disorders. Muscular dystrophies (MDs) are a severe and heterogeneous type of human muscle disease, manifested by progressive muscle wasting and degeneration. The disease pathogenesis and therapeutic options for MDs have been investigated for decades using rodent models, and considerable knowledge has been accumulated on the cause and pathogenetic mechanisms of this group of human disorders. However, due to some differences between disease severity and progression, what is learned in mammalian models does not always transfer to humans, prompting the desire for additional and alternative models. More recently, zebrafish have emerged as a novel and robust animal model for the study of human muscle disease. Zebrafish MD models possess a number of distinct advantages for modeling human muscle disorders, including the availability and ease of generating mutations in homologous disease-causing genes, the ability to image living muscle tissue in an intact animal, and the suitability of zebrafish larvae for large-scale chemical screens. In this chapter, we review the current understanding of molecular and cellular mechanisms involved in MDs, the process of myogenesis in zebrafish, and the structural and functional characteristics of zebrafish larval muscles. We further discuss the insights gained from the key zebrafish MD models that have been so far generated, and we summarize the attempts that have been made to screen for small molecules inhibitors of the dystrophic phenotypes using these models. Overall, these studies demonstrate that zebrafish is a useful in vivo system for modeling aspects of human skeletal muscle disorders. Studies using these models have contributed both to the understanding of the pathogenesis of muscle wasting disorders and demonstrated their utility as highly relevant models to implement therapeutic screening regimens.

The atlas of zebrafish development aims to provide a reference at the gross anatomical level for the zebrafish, identifying the major anatomical structures in samples covering the range of development from the early embryo until adulthood. The atlas is generated using Optical Projection Tomography (OPT), which has a number of advantages such as the ability to produce a complete three-dimensional (3D) model from a single sample. The OPT approach does not provide cellular resolution for the range of sample sizes encompassing the development of zebrafish from embryo to adulthood. This chapter provides the information about the contents and methodology of the atlas as well as a brief description about the interpretation of the images. The tomographic approach requires the sample to be in focus for at least 180° of the rotation and therefore the depth of focus should extend at least half-way into the sample. Image resolution is proportional to the numerical aperture of the objective while the depth of focus is inversely proportional. Therefore, there is a trade-off between resolution and the thickness of the sample; as a result, it is difficult to image at a constant resolution throughout the wide range of sample sizes. A significant advantage of this imaging technique over conventional physical sectioning approaches is that the sample remains intact and distortion of the sample as a result of the cutting and mounting of sections is eliminated.

This chapter describes the major features of the website FishNet, which is an interactive database for zebrafish development. It discusses the pros and cons of each of the digital and print versions. The greatest advantage of the print version is its portable nature, allowing its use in the laboratory or aquarium where access to the Internet resource may not be possible or appropriate, and it is often easier to evaluate images in high-quality prints instead of display technology. However, the website has an edge over the print resource because the complete stage series and all sections within each sample embryo can be accessed through the website. The interactive nature of the website also allows the virtual sectioning of the 3D models at any of the represented stages and to zoom in and out to different image magnifications. It is also possible to view volume or surface renderings of the complete sample that may be manipulated on screen, which are particularly useful for mental conceptualization of anatomical morphology. The benefit of the dynamic nature of the website is the possibility for information to be easily updated, which allows both for addition of further annotations and any modification where necessary. Thus, the delivery of an anatomical resource via the Internet holds a number of advantages over a traditional, printed version.

This chapter describes the induction and patterning of embryonic skeletal muscle cells in the zebrafish. The optical clarity of the zebrafish embryo makes it especially well suited for the application of sophisticated cell labeling techniques, approaches that facilitate the direct visualization of muscle cell ontogeny. The identification of the genes that control this process is well underway following two large-scale mutant screens of the zebrafish genome and these have uncovered numerous mutants that disrupt muscle cell formation and differentiation in various ways. In fish, as in other vertebrates, the skeletal muscle of the trunk and tail derives from a specific embryological compartment, the myotome, which in amniotes has been shown to be induced within the segmented mesoderm of the somite. Somites condense from mesoderm immediately adjacent to the central body axis, the so-called “paraxial mesoderm,” and segment in a stereotypic rostral to caudal progression. The simultaneous development of both muscle layers in the free swimming larvae has been suggested to endow the organism with the abilities to search for food sources at low swimming velocity and to avoid predators by escape at high velocity.