Unexpected role of β-catenin signaling in germ layer specification

By Tatiana Lebedeva and Grigory Genikhovich

What is this?
This video shows early stages of the embryonic development of the sea anemone Nematostella vectensis. In green, you can see the dynamic localization of the β-catenin protein carrying a fluorescent tag. β-catenin is a crucial molecule during embryogenesis, serving a dual role: structurally, it helps cells stick together; functionally, it enters cell nuclei to regulate gene expression. In this video, you can clearly observe glowing cell boundaries and the nuclear translocation of β-catenin in specific embryonic cells at specific developmental stages.

Where can this be found?
In the wild, Nematostella vectensis inhabits shallow coastal waters along North America’s Atlantic coast. Today, it is a popular model organism in developmental biology labs worldwide. This specific fluorescent β-catenin-tagged Nematostella line was developed at the Department of Neuroscience and Developmental Biology, University of Vienna (Austria).

How was this taken?
We used CRISPR/Cas9 genome editing to insert a GFP (Green Fluorescent Protein) sequence into the Nematostella β-catenin gene. After injecting around 35,000 embryos, we successfully identified one male carrying the correct insertion in the germ cells. This allowed us to establish first a heterozygous F1 and then a homozygous F2 generation with “glowing β-catenin” in all cells, enabling detailed developmental imaging. For imaging, embryos were gently immobilized in low-melting agarose and filmed live using a spinning disk confocal microscope at the Medical University of Vienna, with valuable support from the Adameyko lab.

Why should people care about this?

Nematostella belongs to Cnidaria (corals, sea anemones, and jellyfish), a sister group to Bilateria (insects, worms, sea urchins, and humans). In bilaterians, β-catenin signaling activates the formation of the endomesoderm, which soon splits into an endoderm giving rise to the gut tube and its derivatives, and mesoderm forming muscles, reproductive organs, and more. For over two decades, scientists assumed β-catenin had a similar function in cnidarians.

Our study challenges previous assumptions and provides new insights into how animal developmental mechanisms evolved. Upon careful observation, you will notice that in the early embryo, β-catenin enters cell nuclei on one side of the embryo, while later, endomesodermal cells start to invaginate on the opposite side of the embryo, forming its gut. Combined with the existing gene knockdown data, this shows that β-catenin does not specify the endomesoderm in Nematostella, as previously thought, but rather protects non-endomesodermal cells (ectoderm) from becoming the endomesoderm. This unexpected finding highlights an important evolutionary shift, suggesting that using β-catenin to specify the endomesoderm in the embryo was an evolutionary innovation of Bilateria.

Where can people find more about it?
Read our recent paper in Nature Communications: 
https://www.nature.com/articles/s41467-025-57109-w

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