1. Developmental Biology
Download icon

Live imaging of heart tube development in mouse reveals alternating phases of cardiac differentiation and morphogenesis

  1. Kenzo Ivanovitch
  2. Susana Temiño Valbuena
  3. Miguel Torres  Is a corresponding author
  1. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Spain
Research Article
  • Cited 29
  • Views 5,393
  • Annotations
Cite this article as: eLife 2017;6:e30668 doi: 10.7554/eLife.30668

Abstract

During vertebrate heart development two progenitor populations, first and second heart fields (FHF, SHF), sequentially contribute to longitudinal subdivisions of the heart tube (HT), with the FHF contributing the left ventricle and part of the atria, and the SHF the rest of the heart. Here we study the dynamics of cardiac differentiation and morphogenesis by tracking individual cells in live analysis of mouse embryos. We report that during an initial phase, FHF precursors differentiate rapidly to form a cardiac crescent, while limited morphogenesis takes place. In a second phase, no differentiation occurs while extensive morphogenesis, including splanchnic mesoderm sliding over the endoderm, results in HT formation. In a third phase, cardiac precursor differentiation resumes and contributes to SHF-derived regions and the dorsal closure of the HT. These results reveal tissue-level coordination between morphogenesis and differentiation during HT formation and provide a new framework to understand heart development.

Article and author information

Author details

  1. Kenzo Ivanovitch

    Developmental Biology Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  2. Susana Temiño Valbuena

    Developmental Biology Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Miguel Torres

    Developmental Biology Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
    For correspondence
    mtorres@cnic.es
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0906-4767

Funding

Ministerio de Economía y Competitividad (BFU2015-71519-P)

  • Miguel Torres

Instituto de Salud Carlos III (RD16/0011/0019)

  • Miguel Torres

European Molecular Biology Organization (ATL1275-2014)

  • Kenzo Ivanovitch

Human Frontier Science Program (LT000609/2015)

  • Kenzo Ivanovitch

Ministerio de Economía y Competitividad (BFU2015-70193-REDT)

  • Miguel Torres

Ministerio de Economía y Competitividad (SEV-2015-0505)

  • Miguel Torres

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal procedures were approved by the CNIC Animal Experimentation Ethics Committee, by the Community of Madrid (Ref. PROEX 220/15) and conformed to EU Directive 2010/63EU and Recommendation 2007/526/EC regarding the protection of animals used for experimental and other scientific purposes, enforced in Spanish law under Real Decreto 1201/2005.

Reviewing Editor

  1. Richard P Harvey, Victor Chang Cardiac Research Institute, Australia

Publication history

  1. Received: July 23, 2017
  2. Accepted: November 26, 2017
  3. Accepted Manuscript published: December 5, 2017 (version 1)
  4. Version of Record published: December 15, 2017 (version 2)

Copyright

© 2017, Ivanovitch et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 5,393
    Page views
  • 611
    Downloads
  • 29
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Developmental Biology
    2. Neuroscience
    Eduardo Loureiro-Campos et al.
    Research Article

    The transcription factor activating protein two gamma (AP2γ) is an important regulator of neurogenesis both during embryonic development as well as in the postnatal brain, but its role for neurophysiology and behavior at distinct postnatal periods is still unclear. In this work, we explored the neurogenic, behavioral, and functional impact of a constitutive and heterozygous AP2γ deletion in mice from early postnatal development until adulthood. AP2γ deficiency promotes downregulation of hippocampal glutamatergic neurogenesis, altering the ontogeny of emotional and memory behaviors associated with hippocampus formation. The impairments induced by AP2γ constitutive deletion since early development leads to an anxious-like phenotype and memory impairments as early as the juvenile phase. These behavioral impairments either persist from the juvenile phase to adulthood or emerge in adult mice with deficits in behavioral flexibility and object location recognition. Collectively, we observed a progressive and cumulative impact of constitutive AP2γ deficiency on the hippocampal glutamatergic neurogenic process, as well as alterations on limbic-cortical connectivity, together with functional behavioral impairments. The results herein presented demonstrate the modulatory role exerted by the AP2γ transcription factor and the relevance of hippocampal neurogenesis in the development of emotional states and memory processes.

    1. Developmental Biology
    2. Neuroscience
    Benoît Boulan et al.
    Research Article

    Neurodevelopmental axonal pathfinding plays a central role in correct brain wiring and subsequent cognitive abilities. Within the growth cone, various intracellular effectors transduce axonal guidance signals by remodeling the cytoskeleton. Semaphorin-3E (Sema3E) is a guidance cue implicated in development of the fornix, a neuronal tract connecting the hippocampus to the hypothalamus. Microtubule-Associated Protein 6 (MAP6) has been shown to be involved in the Sema3E growth-promoting signaling pathway. In this study, we identified the Collapsin Response Mediator Protein 4 (CRMP4) as a MAP6 partner and a crucial effector in Sema3E growth-promoting activity. CRMP4-KO mice displayed abnormal fornix development reminiscent of that observed in Sema3E-KO mice. CRMP4 was shown to interact with the Sema3E tripartite receptor complex within Detergent-Resistant Membrane (DRM) domains, and DRM domain integrity was required to transduce Sema3E signaling through the Akt/GSK3 pathway. Finally, we showed that the cytoskeleton-binding domain of CRMP4 is required for Sema3E's growth-promoting activity, suggesting that CRMP4 plays a role at the interface between Sema3E receptors, located in DRM domains, and the cytoskeleton network. As the fornix is affected in many psychiatric diseases, such as schizophrenia, our results provide new insights to better understand the neurodevelopmental components of these diseases.