An Eya1-Notch axis specifies bipotential epibranchial differentiation in mammalian craniofacial morphogenesis

  1. Haoran Zhang
  2. Li Wang
  3. Elaine Yee Man Wong
  4. Sze Lan Tsang
  5. Pin-Xian Xu
  6. Urban Lendahl
  7. Mai Har Sham  Is a corresponding author
  1. The University of Hong Kong, Hong Kong
  2. Mount Sinai School of Medicine, United States
  3. Karolinska Institute, Sweden

Abstract

Craniofacial morphogenesis requires proper development of pharyngeal arches and epibranchial placodes. We show that the epibranchial placodes, in addition to giving rise to cranial sensory neurons, generate a novel lineage-related non-neuronal cell population for mouse pharyngeal arch development. Eya1 is essential for the development of epibranchial placodes and proximal pharyngeal arches. We identify an Eya1-Notch regulatory axis that specifies both the neuronal and non-neuronal commitment of the epibranchial placode, where Notch acts downstream of Eya1 and promotes the non-neuronal cell fate. Notch is regulated by the threonine phosphatase activity of Eya1. Eya1 dephosphorylates p-threonine-2122 of the Notch1 intracellular domain (Notch1 ICD), which increases the stability of Notch1 ICD and maintains Notch signaling activity in the non-neuronal epibranchial placodal cells. Our data unveil a more complex differentiation program in epibranchial placodes and an important role for the Eya1-Notch axis in craniofacial morphogenesis.

Article and author information

Author details

  1. Haoran Zhang

    School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  2. Li Wang

    School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  3. Elaine Yee Man Wong

    School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  4. Sze Lan Tsang

    School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  5. Pin-Xian Xu

    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Urban Lendahl

    Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Mai Har Sham

    School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong
    For correspondence
    mhsham@hku.hk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1179-7839

Funding

Research Grants Council, University Grants Committee (RGC GRF 777411)

  • Mai Har Sham

Research Grants Council, University Grants Committee (RGC GRF 17113415)

  • Mai Har Sham

Cancerfonden (SCS X2017-2019,335)

  • Urban Lendahl

Vetenskapsrådet (project grant 2014-2018,RX331)

  • Urban Lendahl

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 mouse experiments were performed in strict accordance with the recommendations and approved by the University of Hong Kong animal research ethics committee (CULATR No. 3329-14 and 3862-15).

Copyright

© 2017, Zhang 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

  • 1,897
    views
  • 298
    downloads
  • 27
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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)

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

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

  1. Haoran Zhang
  2. Li Wang
  3. Elaine Yee Man Wong
  4. Sze Lan Tsang
  5. Pin-Xian Xu
  6. Urban Lendahl
  7. Mai Har Sham
(2017)
An Eya1-Notch axis specifies bipotential epibranchial differentiation in mammalian craniofacial morphogenesis
eLife 6:e30126.
https://doi.org/10.7554/eLife.30126

Share this article

https://doi.org/10.7554/eLife.30126

Further reading

    1. Cell Biology
    2. Developmental Biology
    Heungjin Ryu, Kibum Nam ... Jung-Hoon Park
    Research Article

    In most murine species, spermatozoa exhibit a falciform apical hook at the head end. The function of the sperm hook is not yet clearly understood. In this study, we investigate the role of the sperm hook in the migration of spermatozoa through the female reproductive tract in Mus musculus (C57BL/6), using a deep tissue imaging custom-built two-photon microscope. Through live reproductive tract imaging, we found evidence indicating that the sperm hook aids in the attachment of spermatozoa to the epithelium and facilitates interactions between spermatozoa and the epithelium during migration in the uterus and oviduct. We also observed synchronized sperm beating, which resulted from the spontaneous unidirectional rearrangement of spermatozoa in the uterus. Based on live imaging of spermatozoa-epithelium interaction dynamics, we propose that the sperm hook plays a crucial role in successful migration through the female reproductive tract by providing anchor-like mechanical support and facilitating interactions between spermatozoa and the female reproductive tract in the house mouse.

    1. Developmental Biology
    Michele Bertacchi, Gwendoline Maharaux ... Michèle Studer
    Research Article Updated

    The morphogen FGF8 establishes graded positional cues imparting regional cellular responses via modulation of early target genes. The roles of FGF signaling and its effector genes remain poorly characterized in human experimental models mimicking early fetal telencephalic development. We used hiPSC-derived cerebral organoids as an in vitro platform to investigate the effect of FGF8 signaling on neural identity and differentiation. We found that FGF8 treatment increases cellular heterogeneity, leading to distinct telencephalic and mesencephalic-like domains that co-develop in multi-regional organoids. Within telencephalic regions, FGF8 affects the anteroposterior and dorsoventral identity of neural progenitors and the balance between GABAergic and glutamatergic neurons, thus impacting spontaneous neuronal network activity. Moreover, FGF8 efficiently modulates key regulators responsible for several human neurodevelopmental disorders. Overall, our results show that FGF8 signaling is directly involved in both regional patterning and cellular diversity in human cerebral organoids and in modulating genes associated with normal and pathological neural development.