Zebrafish Models of Human Skeletal Disorders: Embryo and Adult Swimming Together

Abstract

Danio rerio (zebrafish) is an elective model organism for the study of vertebrate development because of its high degree of homology with human genes and organs, including bone. Zebrafish embryos, because of the optical clarity, small size, and fast development, can be easily used in large-scale mutagenesis experiments to isolate mutants with developmental skeletal defects and in high-throughput screenings to find new chemical compounds for the ability to revert the pathological phenotype. On the other hand, the adult zebrafish represents another powerful resource for pathogenic and therapeutic studies about adult human bone diseases. In fish, some characteristics such as bone turnover, reparation, and remodeling of the adult bone tissue cannot be found at the embryonic stage. Several pathological models have been established in adult zebrafish such as bone injury models, osteoporosis, and genetic diseases such as osteogenesis imperfecta. Given the growing interest for metabolic diseases and their complications, adult zebrafish models of type 2 diabetes and obesity have been recently generated and analyzed for bone complications using scales as model system. Interestingly, an osteoporosis-like phenotype has been found to be associated with metabolic alterations suggesting that bone complications share the same mechanisms in humans and fish. Embryo and adult represent powerful resources in rapid development to study bone physiology and pathology from different points of view.

Zebrafish as a model to study autophagy and its role in skeletal development and disease

“…Many human skeletal disorders can be modelled in zebrafish and can recapitulate the phenotypes seen in higher vertebrates. For example, equivalent models for disorders such as osteogenesis imperfecta, scoliosis, osteoporosis, Stickler syndrome, and osteoarthritis are available in zebrafish (Askary et al 2016 ; Carnovali et al 2019 ; Lawrence et al 2018 ; Mackay et al 2013 ). Additionally, as zebrafish develop osteoarthritis naturally during ageing, the pathogenesis of the disease and its common symptoms such as increased spinal deformities, vertebral dislocations, and fractures, and the formation of osteophytes can be easily explored (Hayes et al 2013 ).…”

Zebrafish: A Resourceful Vertebrate Model to Investigate Skeletal Disorders

“…Moreover, due to its rapid growth, a recognizable and complete vertebrate body plan is already in place by 1 day post fertilization (dpf) and embryogenesis is complete by 3 dpf (11). In contrast to other vertebrate models such as rodents, the small size and large number of offspring of zebrafish allow for increased sample numbers, thereby increasing the statistical power of experiments (3). Finally, the relatively low husbandry cost further contributed to the increasing popularity of the zebrafish as a model for research (11).…”

Zebrafish as a Model for Fish Diseases in Aquaculture

“…The zebrafish is extensively used as a vertebrate model for human diseases [1][2][3][4][5][6] and other conditions such as aging, development and genetics [7][8][9][10][11][12][13][14][15][16]. The small fish presents many advantages as a model; therefore, it cannot be overlooked and has not been since Dr. George Streisinger convinced the world in the 1980s of the wonders of the zebrafish [17][18][19].…”