Fish is Fish: the use of experimental model species to reveal causes of skeletal diversity in evolution and disease

Abstract

Summary Fishes are wonderfully diverse. This variety is a result of the ability of ray-finned fishes to adapt to a wide range of environments, and has made them more specious than the rest of vertebrates combined. With such diversity it is easy to dismiss comparisons between distantly related fishes in efforts to understand the biology of a particular fish species. However, shared ancestry and the conservation of developmental mechanisms, morphological features and physiology provide the ability to use comparative analyses between different organisms to understand mechanisms of development and physiology. The use of species that are amenable to experimental investigation provides tools to approach questions that would not be feasible in other ‘non-model’ organisms. For example, the use of small teleost fishes such as zebrafish and medaka has been powerful for analysis of gene function and mechanisms of disease in humans, including skeletal diseases. However, use of these fish to aid in understanding variation and disease in other fishes has been largely unexplored. This is especially evident in aquaculture research. Here we highlight the utility of these small laboratory fishes to study genetic and developmental factors that underlie skeletal malformations that occur under farming conditions. We highlight several areas in which model species can serve as a resource for identifying the causes of variation in economically important fish species as well as to assess strategies to alleviate the expression of the variant phenotypes in farmed fish. We focus on genetic causes of skeletal deformities in the zebrafish and medaka that closely resemble phenotypes observed both in farmed as well as natural populations of fishes.

Revisiting in vivo staining with alizarin red S - a valuable approach to analyse zebrafish skeletal mineralization during development and regeneration

“…The dual visualization of mineralization and GFP expression can be relevant for the documentation of bone pathologies. Indeed, skeletal malformations in fish are a subject of growing interest, related to malformations in farmed fish and to skeletal defects of model fish in the frame of biomedical research [6]. The example of malformed regenerated lepidotrichia shows that deformities can be observed in great detail using ARS staining (Fig.…”

“…In addition, the complete genome sequence and its annotation are available, as well as a broad array of molecular and cellular tools. An increasing number of well characterized fish mutants has been derived from large scale mutagenesis screens ([4–6]; http://www.sanger.ac.uk/resources/zebrafish/zmp/), and many transgenic fish lines have been developed using fluorescent proteins (such as Green Fluorescent Protein - GFP) to report the expression of skeleton-related genes [7]. Recently, the development of reverse genetic approaches, such as TALE nucleases and Crispr/Cas9 systems, opened new horizons for targeted mutagenesis in zebrafish [8].…”

Utility of quantitative micro-computed tomographic analysis in zebrafish to define gene function during skeletogenesis

“…Additionally remodeling of the skeleton is key for the correct shaping of fish bones during development. Zebrafish, medaka and other small laboratory fish models are complementary systems to rodent models for studies of skeletogenesis, with advantages including ease of genetic manipulation, visualization of bone cells in real time during development, the large number of progeny and relatively low cost of husbandry 2,3 .…”

“…Rather, microCT is commonly used as an imaging substitute for whole mount Alizarin red staining (e.g. 2,20 ). In cases where quantification is presented, the intrinsic variation of these quantitative measurements in the zebrafish is unclear (e.g.…”

Workshop report: The medaka model for comparative assessment of human disease mechanisms

“…Presentations at the workshop documented medaka as a valuable comparative model, with the zebrafish, but also, that many newly developed medaka disease models were able to provide more direct translational understating of the human condition for diseases such as osteoporosis (To et al, 2012), xenobiotic induced hepatic fibrosis (Wolf et al, 2005), hypohidrotic ectodermal dysplasia (Harris et al, 2014), high-fat-diet (HFD) induced diabetic nephropathy (Ichimura et al, 2013), and chronic mycobacterial infection (tuberculosis; Mosi et al, 2012. ), to name just a few.…”