Nodal and Planar Cell Polarity signaling cooperate to regulate zebrafish convergence and extension gastrulation movements

  1. Margot L K Williams  Is a corresponding author
  2. Lilianna Solnica-Krezel
  1. Baylor College of Medicine, United States
  2. Washington University School of Medicine, United States

Abstract

During vertebrate gastrulation, convergence & extension (C&E) of the primary anteroposterior (AP) embryonic axis is driven by polarized mediolateral (ML) cell intercalations and is influenced by AP axial patterning. Nodal signaling is essential for patterning of the AP axis while Planar Cell Polarity (PCP) signaling polarizes cells with respect to this axis, but how these two signaling systems interact during C&E is unclear. We find that the neuroectoderm of Nodal-deficient zebrafish gastrulae exhibits reduced C&E cell behaviors, which require Nodal signaling in both cell- and non-autonomous fashions. PCP signaling is partially active in Nodal-deficient embryos and its inhibition exacerbates their C&E defects. Within otherwise naïve zebrafish blastoderm explants, however, Nodal induces C&E in a largely PCP-dependent manner, arguing that Nodal acts both upstream of and in parallel with PCP during gastrulation to cooperatively regulate embryonic axis extension.

Data availability

Sequencing data have been deposited in GEO under accession code GSE147302. Processed RNA-seq data have been provided in Source Data Files 1 & 2

The following data sets were generated

Article and author information

Author details

  1. Margot L K Williams

    Center for Precision Environmental Health, Baylor College of Medicine, Houston, United States
    For correspondence
    Margot.Williams@BCM.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9704-6301
  2. Lilianna Solnica-Krezel

    Department of Developmental Biology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institutes of Health (K99HD091386)

  • Margot L K Williams

National Institute of General Medical Sciences (R35GM118179)

  • Lilianna Solnica-Krezel

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Adult zebrafish were raised and maintained according to established methods and in compliance with standards established by the Washington University Animal Care and Use Committee (IACUC), approval number 20160116; Animal Welfare Assurance number A-3381-01.

Copyright

© 2020, Williams & Solnica-Krezel

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

  • 3,936
    views
  • 556
    downloads
  • 35
    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. Margot L K Williams
  2. Lilianna Solnica-Krezel
(2020)
Nodal and Planar Cell Polarity signaling cooperate to regulate zebrafish convergence and extension gastrulation movements
eLife 9:e54445.
https://doi.org/10.7554/eLife.54445

Share this article

https://doi.org/10.7554/eLife.54445

Further reading

    1. Cancer Biology
    2. Developmental Biology
    Sara Jaber, Eliana Eldawra ... Franck Toledo
    Research Article

    Missense ‘hotspot’ mutations localized in six p53 codons account for 20% of TP53 mutations in human cancers. Hotspot p53 mutants have lost the tumor suppressive functions of the wildtype protein, but whether and how they may gain additional functions promoting tumorigenesis remain controversial. Here, we generated Trp53Y217C, a mouse model of the human hotspot mutant TP53Y220C. DNA damage responses were lost in Trp53Y217C/Y217C (Trp53YC/YC) cells, and Trp53YC/YC fibroblasts exhibited increased chromosome instability compared to Trp53-/- cells. Furthermore, Trp53YC/YC male mice died earlier than Trp53-/- males, with more aggressive thymic lymphomas. This correlated with an increased expression of inflammation-related genes in Trp53YC/YC thymic cells compared to Trp53-/- cells. Surprisingly, we recovered only one Trp53YC/YC female for 22 Trp53YC/YC males at weaning, a skewed distribution explained by a high frequency of Trp53YC/YC female embryos with exencephaly and the death of most Trp53YC/YC female neonates. Strikingly, however, when we treated pregnant females with the anti-inflammatory drug supformin (LCC-12), we observed a fivefold increase in the proportion of viable Trp53YC/YC weaned females in their progeny. Together, these data suggest that the p53Y217C mutation not only abrogates wildtype p53 functions but also promotes inflammation, with oncogenic effects in males and teratogenic effects in females.

    1. Developmental Biology
    Mengjie Li, Aiguo Tian, Jin Jiang
    Research Advance

    Stem cell self-renewal often relies on asymmetric fate determination governed by niche signals and/or cell-intrinsic factors but how these regulatory mechanisms cooperate to promote asymmetric fate decision remains poorly understood. In adult Drosophila midgut, asymmetric Notch (N) signaling inhibits intestinal stem cell (ISC) self-renewal by promoting ISC differentiation into enteroblast (EB). We have previously shown that epithelium-derived Bone Morphogenetic Protein (BMP) promotes ISC self-renewal by antagonizing N pathway activity (Tian and Jiang, 2014). Here, we show that loss of BMP signaling results in ectopic N pathway activity even when the N ligand Delta (Dl) is depleted, and that the N inhibitor Numb acts in parallel with BMP signaling to ensure a robust ISC self-renewal program. Although Numb is asymmetrically segregated in about 80% of dividing ISCs, its activity is largely dispensable for ISC fate determination under normal homeostasis. However, Numb becomes crucial for ISC self-renewal when BMP signaling is compromised. Whereas neither Mad RNA interference nor its hypomorphic mutation led to ISC loss, inactivation of Numb in these backgrounds resulted in stem cell loss due to precocious ISC-to-EB differentiation. Furthermore, we find that numb mutations resulted in stem cell loss during midgut regeneration in response to epithelial damage that causes fluctuation in BMP pathway activity, suggesting that the asymmetrical segregation of Numb into the future ISC may provide a fail-save mechanism for ISC self-renewal by offsetting BMP pathway fluctuation, which is important for ISC maintenance in regenerative guts.