Skip to main content

High Content Screening for Modulators of Cardiovascular or Global Developmental Pathways in Zebrafish

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1263))

Abstract

Major developmental pathways play critical roles in wide array of human pathologies. Chemical genomic screening allows for the discovery of novel tools not only to target known pathway interactors but also to discover new, chemically tractable targets for known pathways. The zebrafish has emerged as a useful model for developmental biology and has been well characterized. The zebrafish represents a hardy conglomerate of totipotent cells that are massively and simultaneously assessing all significant pathways in parallel in an endogenous context. This represents a gold standard for biological assays, chemically targeting select pathways without causing pleiotropic effects. Here, we describe methods used to develop high content screening assays implementing transgenic zebrafish to assess phenotypic changes that have identified several classes of novel compounds that effect developmental pathways.

This is a preview of subscription content, log in via an institution.

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Hisaoka KK (1958) The effects of 2-acetylaminofluorene on the embryonic development of the zebrafish II. Histochemical studies. Cancer Res 18:664–667

    CAS  PubMed  Google Scholar 

  2. Skidmore JF (1965) Resistance to zinc sulphate of the zebrafish (Brachydanio rerio Hamilton-Buchanan) at different phases of its life history. Ann Appl Biol 56:47–53

    Article  CAS  PubMed  Google Scholar 

  3. Choi T-Y et al (2007) Zebrafish as a new model for phenotype-based screening of melanogenic regulatory compounds. Pigment Cell Res 20:120–127

    Article  CAS  PubMed  Google Scholar 

  4. George EL et al (1993) Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development 119:1079–1091

    CAS  PubMed  Google Scholar 

  5. Haffter P et al (1996) The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. Development 123:1–36

    CAS  PubMed  Google Scholar 

  6. Chen JN et al (1996) Mutations affecting the cardiovascular system and other internal organs in zebrafish. Development 123:293–302

    CAS  PubMed  Google Scholar 

  7. Driever W et al (1996) A genetic screen for mutations affecting embryogenesis in zebrafish. Development 123:37–46

    CAS  PubMed  Google Scholar 

  8. Kelsh RN et al (1996) Zebrafish pigmentation mutations and the processes of neural crest. Development 123:369–389

    CAS  PubMed  Google Scholar 

  9. Malicki J et al (1996) Mutations affecting development of the zebrafish retina. Development 123:263–273

    CAS  PubMed  Google Scholar 

  10. Schier AF et al (1996) Mutations affecting the development of the embryonic zebrafish brain. Development 123:165–178

    CAS  PubMed  Google Scholar 

  11. Hao J et al (2008) Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells. PLoS One 3:e2904

    Article  PubMed Central  PubMed  Google Scholar 

  12. Hao J et al (2010) In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors. ACS Chem Biol 5:245–253

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Hao J et al (2013) Selective small molecule targeting β-catenin function discovered by in vivo chemical genetic screen. Cell Rep 4:898–904

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Ni TT et al (2011) Discovering small molecules that promote cardiomyocyte generation by modulating Wnt signaling. Chem Biol 18:1658–1668

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Colanesi S et al (2012) Small molecule screening identifies targetable zebrafish pigmentation pathways. Pigment Cell Melanoma Res 25:131–143

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

C.C.H. is supported by the U.S. NIH/NHLBI (R01HL104040), Veterans Administration Merit Award (101BX000771), and the Cali Family Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Charles C. Hong .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Williams, C.H., Hong, C.C. (2015). High Content Screening for Modulators of Cardiovascular or Global Developmental Pathways in Zebrafish. In: Hempel, J., Williams, C., Hong, C. (eds) Chemical Biology. Methods in Molecular Biology, vol 1263. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2269-7_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2269-7_13

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2268-0

  • Online ISBN: 978-1-4939-2269-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics