Zebrafish and medaka as models for bone research including implications regarding space-related issues

Renn, Jörg; Winkler, Christoph; Schartl, Manfred; Fischer, Reinhard; Goerlich, R.

doi:10.1007/s00709-006-0215-x

Cited by 48 publications

(49 citation statements)

References 62 publications

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“…The corresponding orthologs share significantly similar sequences and expression patterns. These findings indicate that the genetic networks controlling bone formation are highly conserved in all vertebrates (Fisher et al, 2003;Flores et al, 2004;Yan et al, 2005;Renn et al, 2006b;Nemoto et al, 2007).…”

Section: Introductionmentioning

confidence: 74%

Osterix‐mCherry transgenic medaka for in vivo imaging of bone formation

Renn

Winkler

2008

Developmental Dynamics

119

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Intramembranous and chondral bone formation by osteoblasts is found in all vertebrates. The genetic network controlling osteoblast differentiation is highly conserved and regulated by a small number of key factors, including the zinc-finger transcription factor Osterix. Expression analysis of osterix in the teleost model medaka revealed a highly restricted expression in skeletal regions. For in vivo imaging, we generated transgenic medaka expressing mCherry under control of the osterix promoter. We show that the transgene becomes expressed in early osteoblasts, which have not yet mineralized bone matrix, and remains high in matured and mineralizing osteoblasts. Life imaging of transgenic larvae provided insight into the appearance and behavior of early osteoblasts during development of the teleost cranium, vertebrae, and caudal fin. In summary, osterix-mCherry transgenic medaka enable us to analyze osteoblasts during different maturation phases in vivo and represent a unique tool to study osteoblast behavior in vertebrate embryos and adults. Developmental Dynamics 238:241-248, 2009.

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Section: Introductionmentioning

confidence: 74%

Osterix‐mCherry transgenic medaka for in vivo imaging of bone formation

Renn

Winkler

2008

Developmental Dynamics

119

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“…The zebrafish shares many key features of bone formation with humans and other animals (Mari-Beffa et al, 2007;Renn et al, 2006). Dermal bone is found in the fin rays, while endochondral bone is present in the supporting skeleton at the fin base (Bird and Mabee, 2003;Grandel and Schulte-Merker, 1998).…”

Section: Skeletal Patterning and Regenerationmentioning

confidence: 99%

Zebrafish development and regeneration: new tools for biomedical research

Brittijn

Duivesteijn²,

Belmamoune³

et al. 2009

Int. J. Dev. Biol.

148

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Basic research in pattern formation is concerned with the generation of phenotypes and tissues. It can therefore lead to new tools for medical research. These include phenotypic screening assays, applications in tissue engineering, as well as general advances in biomedical knowledge. Our aim here is to discuss this emerging field with special reference to tools based on zebrafish developmental biology. We describe phenotypic screening assays being developed in our own and other labs. Our assays involve: (i) systemic or local administration of a test compound or drug to zebrafish in vivo; (ii) the subsequent detection or "readout" of a defined phenotypic change. A positive readout may result from binding of the test compound to a molecular target involved in a developmental pathway. We present preliminary data on assays for compounds that modulate skeletal patterning, bone turnover, immune responses, inflammation and early-life stress. The assays use live zebrafish embryos and larvae as well as adult fish undergoing caudal fin regeneration. We describe proof-of-concept studies on the localised targeting of compounds into regeneration blastemas using microcarriers. Zebrafish are cheaper to maintain than rodents, produce large numbers of transparent eggs, and some zebrafish assays could be scaled-up into medium and high throughput screens. However, advances in automation and imaging are required. Zebrafish cannot replace mammalian models in the drug development pipeline. Nevertheless, they can provide a cost-effective bridge between cell-based assays and mammalian whole-organism models. KEY WORDS: Danio rerio, zebrafish, high-throughput screening, high-content screeningThis article is part of a special journal issue on "Pattern Formation". In this context, it seems appropriate to ask: 'what benefits to society can come from research into pattern formation?' The answer depends on how "pattern formation" is defined. For our purposes, it includes developmental mechanisms that generate Int. J. Dev. Biol. 53: 835-850 (2009) doi: 10.1387/ijdb.082615sb One is the field of human congenital malformations (the pres-836 S. A. Brittijn et al. ence at birth of anatomical abnormalities). Good examples are human malformations of fingers and toes, some cases of which are linked to mutations in the Hox family of developmental patterning genes (Akarsu et al., 1996;Goodman et al., 1997;Goodman, 2002). Teratology -the study of agents that cause congenital malformations -can be seen as applied pattern formation research. Tissue engineering, a medical research discipline that aims to create replacement tissues for patients who have suffered injury or surgical removal of tissues, is another area where knowledge of pattern formation can be applied. To date, the commonest approach to tissue engineering is to culture autologous cells on a synthetic template (Silva and Mooney, 2004). In the future, however, it may be possible to promote pattern formation by these cells so that they generate selforganised tissues or structures ...

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“…Besides its role in Ca 2ϩ storage, bones are important in supporting the vertebrate body, enabling movement by providing a matrix for the attachment of muscles and tendons and protection of important organs like the brain and heart (27). Skeletal homeostasis is established by balancing bone formation through the activity of osteoblasts and through bone resorption by osteoclasts, processes that exhibit a large extent of evolutionary conservation between fish and mammals (28). We used forward genetic screening in zebrafish to identify genes critically involved in bone formation and identified the single orthologue of mammalian TRPV5/6 as a main regulator of bone formation and transepithelial Ca 2ϩ uptake, establishing an in vivo model for this essential physiological process.…”

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confidence: 99%

Trpv5/6 is vital for epithelial calcium uptake and bone formation

et al. 2011

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Calcium is an essential ion serving a multitude of physiological roles. Aside from its role as a second messenger, it is an essential component of the vertebrate bone matrix. Efficient uptake and storage of calcium are therefore indispensable for all vertebrates. Transient receptor potential family, vanilloid type (TRPV)5 and TRPV6 channels are known players in transcellular calcium uptake, but the exact contribution of this pathway is unclear. We used forward genetic screening in zebrafish (Danio rerio) to identify genes essential in bone formation and identified a lethal zebrafish mutant (matt-und-schlapp) with severe defects in bone formation, including lack of ossification of the vertebral column and craniofacial structures. Mutant embryos show a 68% reduction in calcium content, and systemic calcium homeostasis is disturbed when compared with siblings. The phenotype can be partially rescued by increasing ambient calcium levels to 25 mM. We identified the mutation as a loss-of-function mutation in the single orthologue of TRPV5 and 6, trpv5/6. Expression in HEK293 cells showed that Trpv5/6 is a calcium-selective channel capable of inward calcium transport at physiological concentrations whereas the mutant channel is not. Taken together, this study provides both genetic and functional evidence that transcellular epithelial calcium uptake is vital to sustain life and enable bone formation.-Vanoevelen, J., Janssens, A., Huitema, L. F. A., Hammond, C. L., Metz, J. R., Flik, G., Voets, T., Schulte-Merker, S. Trpv5/6 is vital for epithelial calcium uptake and bone formation. FASEB J. 25, 000 -000 (2011). www.fasebj.org

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Zebrafish and medaka as models for bone research including implications regarding space-related issues

Cited by 48 publications

References 62 publications

Osterix‐mCherry transgenic medaka for in vivo imaging of bone formation

Osterix‐mCherry transgenic medaka for in vivo imaging of bone formation

Zebrafish development and regeneration: new tools for biomedical research

Trpv5/6 is vital for epithelial calcium uptake and bone formation

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