MZG

Magdalena Zernicka-Goetz Group

Physiology, Development and Neuroscience

Mammalian Embryo and Stem Cell Group

Human aneuploidies associated with impaired early development

Developmental potential of aneuploid human embryos cultured beyond implantation - This image shows 5 human embryos of different karyotypes: from the top and left to right: Euploid embryo, trisomy 16 embryo, trisomy 15 embryo, monosomy 21 embryo and trisomy 16 embryo. Shahbazi M et al., 2020 Nature

We investigated the developmental potential of human embryos harboring single whole-chromosome aneuploidies by culturing trisomy and monosomy embryos through implantation to Day 9 post-fertilization. We found little differences in cell numbers and lineage ratios in trisomy 15 and 21 embryos but found that monosomy 21 embryos generally arrest during post-implantation development. Interestingly, we found that trisomy 16 embryos had a specific trophoblast hypo-proliferation defect. Using trophoblast stem cells as a model, we showed that overexpression of ECAD leads to cell cycle arrest and terminal differentiation of human trophoblast. We also identified some cases of mosaicism that were misdiagnosed in PGT-A.

Autophagy mediated apoptosis eliminates aneuploid cells in a mouse model of chromosome mosaicism

Links to refine the embryonic cell population and ensure only chromosomally fit cells proceed through development of the fetus.

Singla, S., 2020 Nature communications

In this study Singla et al. find that aneuploid cells are eliminated throughout peri-and early post-implantation development in a mouse model of chaotic aneuploid mosaicism (figure above indicates how diploid-aneuploid mosaic embryos have a reduced proportion of aneuploid (red/mTmG) cells). Aneuploid cells die through p53-mediated apoptosis, in response to increased proteotoxic stress and upregulation of autophagy.

Basement membrane remodelling regulates mouse embryogenesis

Our results indicate a close link between aneuploidy, autophagy, and apoptosis to refine the embryonic cell population and ensure only chromosomally fit cells proceed through development of the fetus. Kyprianou, C. et al, 2020. Nature

The basement membrane (cyan) under the visceral endoderm layer (red nuclei) in the early post-implantation mouse embryo is perforated to allow embryo growth and facilitate primitive streak progression during gastrulation. Artwork by Andreas Karpasitis.

How are experimental models shaping our understanding of early mammalian developement?

Deconstructing and reconstructing the mouse and human early embryo. Shahbazi, M and Zernicka-Goetz, M. 2018. Nature Cell Biology

A timely review on the post-implantation mammalian embryo and how recent technologies have helped to investigate form and function during development. We explore the complex processes of embryogenesis and the multiple regulatory levels involved.

In The Press:

A Perspective Series Investigating The Future of Fertility

An original series on the Future of Fertility by OZY looks at where science is headed — and who’s leading the charge.

Celebrating women in science: a new profile of the work in our lab examines our attempts to solve the mysteries of the embryo. Written by science journalist, Marissa Fessenden. Click here to view the story.

Illustration by Zoe Van Dijk.

The Dance of Life:

Symmetry, Cells and How we Become Human

A new book by Magdalena Zernicka-Goetz and Roger Highfield Published July 2019. A moving celebration of the balletic beauty of life’s beginnings.

The Dance of Life will take you inside the incredible world of life just as it begins and reveals the wonder of the earliest and most profound moments in how we become human. Through Magda’s trailblazing research as a professor at Cambridge you’ll learn how early life starts to take shape and discover the true beauty of life’s beginnings.

Further details here: https://www.penguin.co.uk/books/111/1116560/the-dance-of-life/9780753552926.html

REVIEW: Self-organization of stem cells into embryos: A window on early mammalian development

Organoids and development: A new review published in Science by Marta Shahbazi, Eric Siggia, and Magdalena Zernicka-Goetz.

Here, we review the principles of self-organization and how they set cells in motion to create an embryo. For full access, click on links below:

Abstract: http://science.sciencemag.org/cgi/content/abstract/

Reprint: http://science.sciencemag.org/cgi/rapidpdf/

Full text: http://science.sciencemag.org/cgi/content/full/

Stem Cell Derived Blastocyst Offers a New Way to Study Early Development

Deconstructing and reconstructing the mouse early embryo.

Sozen et al., 2019; Developmental cell

The way the the blastocyst organize itself has profound implications for pregnancy. Our new study shows morphogenetic and transcriptome profiling analyses to reveal how synthetic blastocysts form distinct embryonic-abembryonic axes and primitive endoderm differentiation and can initiate the transition from the pre- to post-implantation egg cylinder morphology in vitro. These studies will help us to better understand the very beginnings of life.