Scientists from Helmholtz Zentrum München revise the current textbook knowledge about gastrulation, the formation of the basic body plan during embryonic development. Their study in mice has implications for cell replacement strategies and cancer research.

Gastrulation is the formation of the three principal germ layers – endoderm, mesoderm and ectoderm. Understanding the formation of the basic body plan is not only important to reveal how the fertilized egg gives rise to an adult organism, but also how congenital diseases arise. In addition, gastrulation serves as the basis to understand processes during embryonic development called epithelial-to-mesenchymal transition which is known to lead to cancer metastasis in adulthood when dysregulated.

“The famous biologist Lewis Wolpert once said that it is not birth, marriage or death, but gastrulation which is truly the most important time of our life. However, there are many things we still don’t know about this phenomenon,” says study leader Heiko Lickert.

In a new study, researchers could show that the formation of the endoderm germ layer is driven by a different mechanism than it has been assumed for a long time. In contrast to the mesoderm, which undergoes an epithelial-to-mesenchymal transition, the endoderm forms independent of this process. The researchers revealed that its formation is regulated by mechanisms of epithelial cell plasticity that allows cells to leave an epithelium and migrate away. During this process, a gene regulatory protein shields the endoderm from undergoing a mesenchymal transition.

A better understanding of endoderm formation has the potential to advance cell replacement therapy (by improving stem cell differentiation into endoderm in vitro). Moreover, epithelial cell plasticity might be an alternative mechanism of cancer cell metastasis and further studies could identify novel targets for therapeutic intervention.

“Our study has not only revealed further details of germ layer formation, but also has broader implications for stem cell differentiation and cancer metastasis of the most common and deadliest cancers worldwide,” explains first author Katharina Scheibner.
 

About the people
Heiko Lickert is Director of the Institute for Diabetes and Regeneration Research at Helmholtz Zentrum München, Professor of Beta Cell Biology at TUM School of Medicine and researcher at the German Center for Diabetes Research (DZD). Katharina Scheibner is a Postdoc at Helmholtz Zentrum München who shared first-authorship with Silvia Engert and Ingo Burtscher.

Original publication:
Scheibner, Schirge, Burtscher et al., 2021: Epithelial cell plasticity drives endoderm formation during gastrulation. Nature Cell Biology, DOI: 10.1038/s41556-021-00694-x

Helmholtz Zentrum München
The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. www.helmholtz-muenchen.de/en