Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Reply to: Zebrafish prrx1a mutants have normal hearts

The Original Article was published on 23 September 2020

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: prrx1a-crispant embryos show mesocardia and a smaller atrium without early defects in the LRO.
Fig. 2: EMT transcription factors in heart laterality in zebrafish.

Data availability

All of the raw data that support the findings of this study are available within the manuscript and its associated files. Source data are provided with this paper.

References

  1. 1.

    Ocaña, O. H. et al. A right-handed signalling pathway drives heart looping in vertebrates. Nature 549, 86–90 (2017).

    Article  ADS  Google Scholar 

  2. 2.

    Tessadori, F. et al. Zebrafish prrx1a mutants have normal hearts. Nature https://doi.org/10.1038/s41586-020-2674-1 (2020).

  3. 3.

    Collignon, J., Varlet, I. & Robertson, E. J. Relationship between asymmetric nodal expression and the direction of embryonic turning. Nature 381, 155–158 (1996).

    CAS  Article  ADS  Google Scholar 

  4. 4.

    Long, S., Ahmad, N. & Rebagliati, M. The zebrafish nodal-related gene southpaw is required for visceral and diencephalic left-right asymmetry. Development 130, 2303–2316 (2003).

    CAS  Article  Google Scholar 

  5. 5.

    Montague, T. G., Gagnon, J. A. & Schier, A. F. Conserved regulation of Nodal-mediated left–right patterning in zebrafish and mouse. Development 145, dev171090 (2018).

    Article  Google Scholar 

  6. 6.

    Hoshijima, K. et al. Highly efficient CRISPR–Cas9-based methods for generating deletion mutations and F0 embryos that lack gene function in zebrafish. Dev. Cell 51, 645–657 (2019).

    CAS  Article  Google Scholar 

  7. 7.

    Vakulskas, C. A. et al. A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells. Nat. Med. 24, 1216–1224 (2018).

    CAS  Article  Google Scholar 

  8. 8.

    Barske, L. et al. Competition between Jagged-Notch and endothelin1 signaling selectively restricts cartilage formation in the zebrafish upper face. PLoS Genet. 12, e1005967 (2016).

    Article  Google Scholar 

  9. 9.

    Noël, E. S. et al. A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality. Nat. Commun. 4, 2754 (2013).

    Article  ADS  Google Scholar 

  10. 10.

    Grimes, D. T. et al. Left–right asymmetric heart jogging increases the robustness of dextral heart looping in zebrafish. Dev. Biol. 459, 79–86 (2020).

    CAS  Article  Google Scholar 

  11. 11.

    El-Brolosy, M. A. et al. Genetic compensation triggered by mutant mRNA degradation. Nature 568, 193–197 (2019).

    CAS  Article  ADS  Google Scholar 

  12. 12.

    Ma, Z. et al. PTC-bearing mRNA elicits a genetic compensation response via Upf3a and COMPASS components. Nature 568, 259–263 (2019).

    CAS  Article  ADS  Google Scholar 

  13. 13.

    Pasek, S., Risler, J. L. & Brézellec, P. The role of domain redundancy in genetic robustness against null mutations. J. Mol. Biol. 362, 184–191 (2006).

    CAS  Article  Google Scholar 

  14. 14.

    Ocaña, O. H. et al. Metastatic colonization requires the repression of the epithelial–mesenchymal transition inducer Prrx1. Cancer Cell 22, 709–724 (2012).

    Article  Google Scholar 

  15. 15.

    Taber, L. A., Voronov, D. A. & Ramasubramanian, A. The role of mechanical forces in the torsional component of cardiac looping. Ann. NY Acad. Sci. 1188, 103–110 (2010).

    Article  ADS  Google Scholar 

  16. 16.

    Domínguez, J. N., Meilhac, S. M., Bland, Y. S., Buckingham, M. E. & Brown, N. A. Asymmetric fate of the posterior part of the second heart field results in unexpected left/right contributions to both poles of the heart. Circ. Res. 111, 1323–1335 (2012).

    Article  Google Scholar 

  17. 17.

    Rago, L. et al. MicroRNAs establish the right-handed dominance of the heart laterality pathway in vertebrates. Dev. Cell 51, 446–459 (2019).

    CAS  Article  Google Scholar 

  18. 18.

    Tautz, D. Redundancies, development and the flow of information. BioEssays 14, 263–266 (1992).

    CAS  Article  Google Scholar 

  19. 19.

    Garrec, J. F. et al. A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics. eLife 6, e28951 (2017).

    Article  Google Scholar 

Download references

Acknowledgements

Work in the laboratory is supported by grants from the Ministry of Science and Innovation through the Spanish State Research Agency (AEI) (MICIU RTI2018-096501-B-I00) and from Generalitat Valenciana (PROMETEOII/2017/150). M.A.N. also acknowledges the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (SEV-2017-0273) to Instituto de Neurociencias.

Author information

Affiliations

Authors

Contributions

N.C. performed the majority of the experiments, analysed the data and prepared the figures; L.R. performed CRISPR injections and collaborated on the scoring of heart positioning; and A.A. performed bioinformatics analyses. N.C., L.R. and A.A. did not contribute to the original publication but they contributed to this Matters Arising, mainly because O.H.O. and H.C., the main authors of the previous study, moved to the National Centre for Cardiovascular Diseases (CNIC, Spain) and Harvard University, respectively. C. Minguillón, P. Murawala, E. M. Tanaka and R. Muñoz-Chápuli, the other co-authors of the previous study1, did not contribute to the issues raised in this Reply. They have been informed, and agreed. J.G. designed the CRISPR guides and performed the mutant selection. M.A.N. conceived the study, interpreted the data and wrote the manuscript.

Corresponding author

Correspondence to M. Angela Nieto.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

This file contains Supplementary Methods.

Reporting Summary

Source data

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Castroviejo, N., Ocaña, O.H., Rago, L. et al. Reply to: Zebrafish prrx1a mutants have normal hearts. Nature 585, E17–E19 (2020). https://doi.org/10.1038/s41586-020-2675-0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing