1. Developmental Biology
  2. Evolutionary Biology
Download icon

Wnt/β-catenin signaling is an evolutionarily conserved determinant of chordate dorsal organizer

  1. Iryna Kozmikova  Is a corresponding author
  2. Zbynek Kozmik
  1. Institute of Molecular Genetics of the ASCR, Czech Republic
Research Article
  • Cited 2
  • Views 2,028
  • Annotations
Cite this article as: eLife 2020;9:e56817 doi: 10.7554/eLife.56817


Deciphering the mechanisms of axis formation in amphioxus is a key step to understanding the evolution of chordate body plan. The current view is that Nodal signaling is the only factor promoting the dorsal axis specification in the amphioxus whereas Wnt/β-catenin signaling plays no role in this process. Here, we re-examined the role of Wnt/βcatenin signaling in the dorsal/ventral patterning of amphioxus embryo. We demonstrated that the spatial activity of Wnt/β-catenin signaling is located in presumptive dorsal cells from cleavage to gastrula stage, and provided functional evidence that Wnt/β-catenin signaling is necessary for the specification of dorsal cell fate in a stage-dependent manner. Microinjection of Wnt8 and Wnt11 mRNA induced ectopic dorsal axis in neurulae and larvae. Finally, we demonstrated that Nodal and Wnt/β-catenin signaling cooperate to promote the dorsal-specific gene expression in amphioxus gastrula. Our study reveals high evolutionary conservation of dorsal organizer formation in the chordate lineage.

Article and author information

Author details

  1. Iryna Kozmikova

    Laboratory of Transcriptional Regulation, Institute of Molecular Genetics of the ASCR, Prague, Czech Republic
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7861-9802
  2. Zbynek Kozmik

    Laboratory of Transcriptional Regulation, Institute of Molecular Genetics of the ASCR, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.


Grantová Agentura České Republiky (GACR 15-21285J)

  • Iryna Kozmikova

Grantová Agentura České Republiky (GACR 17-15374S)

  • Zbynek Kozmik

Ministerstvo Školství, Mládeže a Tělovýchovy (ERDF,project No. CZ.02.1.01/0.0/0.0/16_013/0001775)

  • Iryna Kozmikova

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

Reviewing Editor

  1. Roel Nusse, Stanford University, United States

Publication history

  1. Received: March 10, 2020
  2. Accepted: May 25, 2020
  3. Accepted Manuscript published: May 26, 2020 (version 1)
  4. Accepted Manuscript updated: May 27, 2020 (version 2)
  5. Version of Record published: June 12, 2020 (version 3)


© 2020, Kozmikova & Kozmik

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.


  • 2,028
    Page views
  • 331
  • 2

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

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. Chromosomes and Gene Expression
    2. Developmental Biology
    Rozenn Riou et al.
    Research Article

    Erythropoietin (EPO) is a key regulator of erythropoiesis. The embryonic liver is the main site of erythropoietin synthesis, after which the kidney takes over. The adult liver retains the ability to express EPO, and we discovered here new players of this transcription, distinct from the classical hypoxia-inducible factor pathway. In mice genetically-invalidated in hepatocytes for the chromatin remodeler Arid1a, and for Apc, the major silencer of Wnt pathway, chromatin was more accessible and histone marks turned into active ones at the Epo downstream enhancer. Activating β-catenin signaling increased binding of Tcf4/β-catenin complex and upregulated its enhancer function. The loss of Arid1a together with β-catenin signaling, resulted in cell-autonomous EPO transcription in mouse and human hepatocytes. In mice with Apc-Arid1a gene invalidations in single hepatocytes, Epo de novo synthesis led to its secretion, to splenic erythropoiesis and to dramatic erythrocytosis. Thus, we identified new hepatic EPO regulation mechanism stimulating erythropoiesis.

    1. Developmental Biology
    2. Neuroscience
    Amir Rattner et al.
    Tools and Resources

    In the hippocampus, a widely accepted model posits that the dentate gyrus improves learning and memory by enhancing discrimination between inputs. To test this model, we studied conditional knockout mice in which the vast majority of dentate granule cells (DGCs) fail to develop – including nearly all DGCs in the dorsal hippocampus – secondary to eliminating Wntless (Wls) in a subset of cortical progenitors with Gfap-Cre. Other cells in the Wlsfl/-;Gfap-Cre hippocampus were minimally affected, as determined by single nucleus RNA sequencing. CA3 pyramidal cells, the targets of DGC-derived mossy fibers, exhibited normal morphologies with a small reduction in the numbers of synaptic spines. Wlsfl/-;Gfap-Cre mice have a modest performance decrement in several complex spatial tasks, including active place avoidance. They were also modestly impaired in one simpler spatial task, finding a visible platform in the Morris water maze. These experiments support a role for DGCs in enhancing spatial learning and memory.