Zebrafish: An Emerging Model for Orthopedic Research

Busse, Björn; Galloway, Jenna L.; Gray, Ryan S.; Harris, Matthew P.; Kwon, Ronald Y.

doi:10.1002/jor.24539

Cited by 59 publications

(57 citation statements)

References 134 publications

(170 reference statements)

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“…Scans were acquired at 40 kV and 240 μA with a 0.25 mm aluminum filter. Ring artifacts and beam hardening corrections were the same for all scans, during reconstruction with NRecon software (Bruker) according to previously established protocols (Busse et al, 2019;Fiedler et al, 2018;Suniaga et al, 2018).…”

Section: X-ray and µCt Analysesmentioning

confidence: 99%

FGFR3 is a positive regulator of osteoblast expansion and differentiation during zebrafish skull vault development

Dambroise

Ktorza

Brombin

et al. 2020

Preprint

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AbstractGain- or loss-of-function mutations in fibroblast growth factor receptor 3 (FGFR3) result in cranial vault defects - highlighting the protein’s role in membranous ossification. Zebrafish express high levels of fgfr3 during skull development; in order to study FGFR3’s role in cranial vault development, we generated the first fgfr3 loss-of-function zebrafish (fgfr3lof/lof). The mutant fish exhibited major changes in the craniofacial skeleton, with a lack of sutures, abnormal frontal and parietal bones, and the presence of ectopic bones. Integrated analyses (in vivo imaging, and single-cell RNA sequencing of the osteoblast lineage) of zebrafish fgfr3lof/lof revealed a delay in osteoblast expansion and differentiation, together with changes in the extracellular matrix. These findings demonstrate that fgfr3 is a positive regulator of osteogenesis. We hypothesize that changes in the extracellular matrix within growing bone impair cell-cell communication, mineralization, and new osteoblast recruitment.

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Section: X-ray and µCt Analysesmentioning

confidence: 99%

FGFR3 is a positive regulator of osteoblast expansion and differentiation during zebrafish skull vault development

Dambroise

Ktorza

Brombin

et al. 2020

Preprint

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“…The zebrafish Danio rerio is the most common fish species in biomedical research, including orthopedics (Busse et al, 2020). Important advantages of this organism are a powerful set of genetic tools and an efficient maintenance in a laboratory facility.…”

Section: Introductionmentioning

confidence: 99%

Hydrodynamic stress and phenotypic plasticity of the zebrafish regenerating fin

Dagenais

Blanchoud

Pury

et al. 2021

Preprint

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Understanding how extrinsic factors modulate genetically encoded information to produce a specific phenotype is of prime scientific interest. In particular, the feedback mechanism between abiotic forces and locomotory organs during morphogenesis to achieve efficient movement is a highly relevant example of such modulation. The study of this developmental process can provide unique insights on the transduction of cues at the interface between physics and biology. Here, we take advantage of the natural ability of adult zebrafish to regenerate their amputated fins to assess its morphogenic plasticity upon external modulations. Using a variety of surgical and chemical treatments, we are able to induce phenotypic responses to the structure of the fin. In particular, fin cleft depth and the bifurcation of the bony rays are modulated by the surface area of the stump. To dissect the role of mechanotransduction in this process, we investigate the patterns of hydrodynamic forces acting on the surface of a zebrafish fin during regeneration by using particle tracking velocimetry on a range of biomimetic hydrofoils. This experimental approach enables us to quantitatively compare hydrodynamic stress distributions over flapping fins of varying sizes and shapes. As a result, viscous shear stress acting on the tip of the fin and the resulting internal tension are proposed as suitable signals for guiding the regulation of ray growth dynamics and branching pattern. Our findings suggest that mechanical forces are involved in the fine-tuning of the locomotory organ during fin morphogenesis.

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“…Zebrafish have increasingly become an established model organism for the study of musculoskeletal development and associated disorders (Busse et al, 2019). Zebrafish have also become a premier animal model for mechanistic studies of scoliosis and vertebral malformations as a consequence of defects of the notochord sheath via analyses of mutations in the collagen VIIIa1a (col8a1a) gene (Gray et al, 2014) or defects in the biogenesis of notochord vacuoles (Bagwell et al, 2020;Ellis et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Postembryonic screen for mutations affecting spine development in zebrafish

Gray

González

Ackerman

et al. 2020

Preprint

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The spinal vertebral column gives structural support for the adult body plan, protects the spinal cord, and provides muscle attachment and stability, which allows the animal to move within its environment. The development and maturation of the spine and its physiology involve the integration of multiple musculoskeletal tissues including bone, cartilage, and fibrocartilaginous joints, as well as innervation and control by the nervous system. One of the most common disorders of the spine in human is adolescent idiopathic scoliosis (AIS), which is characterized by the onset of an abnormal lateral curvature of the spine of <10° around adolescence, in otherwise healthy children. The genetic basis of AIS is largely unknown. Systematic genome-wide mutagenesis screens for embryonic phenotypes in zebrafish have been instrumental in the understanding of early patterning of embryonic tissues necessary to build and pattern the embryonic spine. However, the mechanisms required for postembryonic maturation and homeostasis of the spine remain poorly understood. Here we report the results from a small-scale forward genetic screen for adult-viable recessive and dominant mutant zebrafish, displaying overt morphological abnormalities of the adult spine. Germline mutations induced with N-ethyl N-nitrosourea (ENU) were transmitted and screened for dominant phenotypes in 1,229 F1 animals, and subsequently bred to homozygosity in F3 families, from these, 314 haploid genomes were screened for recessive phenotypes. We cumulatively found 39 adult-viable (3 dominant and 36 recessive) mutations each leading to a defect in the morphogenesis of the spine. The largest phenotypic group displayed larval onset axial curvatures, leading to whole-body scoliosis without vertebral dysplasia in adult fish. Pairwise complementation testing within this phenotypic group revealed at least 16 independent mutant loci. Using massively-parallel whole genome or whole exome sequencing and meiotic mapping we defined the molecular identity of several loci for larval onset whole-body scoliosis in zebrafish. We identified a new mutation in the skolios/kinesin family member 6 (kif6) gene, causing neurodevelopmental and ependymal cilia defects in mouse and zebrafish. We also report several recessive alleles of the scospondin and a disintegrin and metalloproteinase with thrombospondin motifs 9 (adamts9) genes, which all display defects in spine morphogenesis. Many of the alleles characterized thus far are non-synonymous mutations in known essential scospondin and adamts9 genes. Our results provide evidence of monogenic traits that are critical for normal spine development in zebrafish, that may help to establish new candidate risk loci for spine disorders in humans.

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Zebrafish: An Emerging Model for Orthopedic Research

Cited by 59 publications

References 134 publications

FGFR3 is a positive regulator of osteoblast expansion and differentiation during zebrafish skull vault development

FGFR3 is a positive regulator of osteoblast expansion and differentiation during zebrafish skull vault development

Hydrodynamic stress and phenotypic plasticity of the zebrafish regenerating fin

Postembryonic screen for mutations affecting spine development in zebrafish

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