An epiblast is a part of the early embryo during embryonic development in mammals. Breaking the symmetry of anterior-posterior (AP) in mammals occurs during the process of gastrulation. So far, the underlying signaling network has been investigated in mice. However, information on the human AP axis formation process have not been available so far.

For their work, researchers led by Dr. Mijo Simunovic and colleagues from the Brivanlou and Siggia laboratories at Rockefeller University in New York City used human embryonic stem cells (hESC) in an optimized matrigel to generate an 3D model of a human epiblast. In size, cell polarity and gene expression, the hESC colonies were  simular to those of a real 10-day human epiblast.

In contrast to conventional cultures in a pure matrigel, the cells formed an approximately spherical hollow shell and produced key biomarkers such as SOX2, OCT4 and NANOG in the optimized culture. NANOG is an important transcription factor involved in the control of stem cell self-renewal.

The scientists observed that a certain dose of a protein called BMP4 led to the spontaneously breakthrough of the axial symmetry and triggered markers for the formation of the primitive stripe as well as the transition from the epithelial into the mesenchymal development. After gene knockouts and with the help of live cell imaging, the scientists have shown that WNT3 and its inhibitor DKK1 downstream of BMP4 played a key role in this process.

With their model of a human epiblast they were able to simulate a breakthrough of the axial symmetry  without extra embryonic tissue or maternal influences.

The scientists have published their work in the journal biorxiv:
Mijo Simunovic, Jakob J. Metzger, Fred Etoc, Anna Yoney, Albert Ruzo, Iain Martyn, Gist Croft, Ali H. Brivanlou & Eric D. Siggia (2018). Molecular mechanism of symmetry breaking in a 3D model of a human epiblast. doi: https://doi.org/10.1101/330704

Source:
https://www.news-medical.net/whitepaper/20190320/Using-Hydrogels-to-Produce-an-Epiblast-3D-Model.aspx