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Zebrafish prrx1a mutants have normal hearts

Nature volume 585, pages E14–E16 (2020)Cite this article

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Matters Arising to this article was published on 23 September 2020

The Original Article was published on 07 September 2017

arising from O. H. Ocaña et al. Nature https://doi.org/10.1038/nature23454 (2017)

How organ laterality is established during embryo development is an intriguing question that remains largely unresolved. By using morpholino-based knockdown and CRISPR–Cas9-induced somatic mutations in zebrafish embryos, Ocaña et al.1 reported a role for the paired-like homeobox transcription factor Prrx1a in a novel right-handed signalling pathway that drives cardiac looping. We analysed this process in two previously described frameshift prrx1a-mutant alleles2, as well as in three newly generated large-deletion alleles that remove exon 1 and upstream sequences around the transcriptional start site (TSS), or the entire locus of the prrx1a gene such that no mRNA is produced. Homozygosity of any of these five alleles does not affect cardiac looping, which calls into question the requirement for prrx1a in left–right (L–R) patterning and cardiac development.

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Fig. 1: Cardiac laterality in prrx1a-mutant embryos.
Fig. 2: Induction of off-target laterality phenotypes by injection of prrx1a-MO1.

Data availability

All data are available within the manuscript and its associated files. Source data are provided with this paper.

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Acknowledgements

We acknowledge support from the Dutch Heart Foundation grant CVON2014-18 CONCOR-GENES to J.B. and the National Institute of Health grants NIH R35 DE027550 to J.G.C., NIH R00 DE024190 to J.T.N. (National Institute of Dental and Craniofacial Research, NIDCR) and NIH R00 DE026239 to L.B. (NIDCR).

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Author notes

  1. Lindsey Barske

    Present address: Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

  2. Lindsey Barske

    Present address: Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

  3. These authors contributed equally: Dennis E. M. de Bakker, Lindsey Barske

Authors and Affiliations

  1. Hubrecht Institute–KNAW and University Medical Centre Utrecht, Utrecht, The Netherlands

    Federico Tessadori, Dennis E. M. de Bakker, Hermine A. Algra, Sven Willekers & Jeroen Bakkers

  2. Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, W. M. Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Lindsey Barske, Nellie Nelson & J. Gage Crump

  3. Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    James T. Nichols

  4. Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands

    Jeroen Bakkers

  5. Department of Pediatric Cardiology, Division of Pediatrics, University Medical Center Utrecht, Utrecht, The Netherlands

    Jeroen Bakkers

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  1. Federico Tessadori
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Contributions

F.T.: project conception, experimental work, data analysis, manuscript writing; D.E.M.d.B.: project conception, experimental work; L.B.: experimental work, data analysis, manuscript revision; N.N.: experimental work, data analysis; H.A.A.: experimental work, data analysis; S.W.: experimental work; J.T.N.: zebrafish lines, manuscript revision; J.G.C.: zebrafish lines, project conception, manuscript writing; J.B.: project conception, manuscript writing.

Corresponding authors

Correspondence to J. Gage Crump or Jeroen Bakkers.

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Tessadori, F., de Bakker, D.E.M., Barske, L. et al. Zebrafish prrx1a mutants have normal hearts. Nature 585, E14–E16 (2020). https://doi.org/10.1038/s41586-020-2674-1

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