Magdalena Zernicka-Goetz PhD
Magdalena is Professor of Developmental Biology in the Department of Physiology, Development and Neuroscience.
Cell fate specification and developmental plasticity in the mouse embryo
Co-workers: Stoyana Alexandrova • Paula Almeida Coelho • Ivan Bedzhov • Monika Bialecka • Helen Bolton • Leah Bury • Andy Cox • John Crang • • Mohammed Goolam • Sarah Graham • Agnieszka Jedrusik • Chuen Yan Leung • Maryna Panamoarova • Amelia Thompson • Anoeska van de Moosdijk • Krzysztof Wicher • Agata Zielinksa
Plain English: We study the development of the mouse embryo because it is an excellent model for the human embryo. In contrast to embryos of most non-mammalian species where development follows a fixed set of instructions, cell fate is flexible in mammalian embryos enabling them to recover from perturbations. However, early mammalian embryos do not appear to be simply a uniform balls of cells; their cells do show some preferences for adopting certain positions that will in turn govern what they develop into. We are looking at how cells come to occupy different positions within the embryo and how this influences their development to activate sets of molecular switches. We also want to know whether and how “forcing” a cell along a particular developmental pathway will cause it to move to a place more suited to its new way of life. Although the embryo appears quite primitive before it has implanted into the wall of the mother’s womb, in fact it comprises some four cell-types. A few cells from one cell-type will develop into a cluster that shortly after implantation will send out the signal to make the head-end of the body. We wish to know the origins of these cells and how their development is influenced by surrounding structures.
The mouse embryo provides an excellent model for studying mammalian development, including our own. It is also an excellent model to discover how to guide the differentiation of pluripotent cells towards specialised cell types. Initially mouse embryo cells are pluripotent and able to make any cell in the foetus or placenta but gradually this ability becomes restricted. The major focus of our group is to uncover the progressive cell fate transitions critical for generating pluripotent cells on one hand and cells that differentiate on the other, and how these transitions are coordinated with development of the embryo’s unique form. We are particularly interested in a group of pluripotent cells, the epiblast, that is able to generate any cell type and indeed will form the entire body. We aim to understand how these cells are first set apart to prevent their differentiation while their neighbours enter differentiation pathways and, once this is achieved, how the distinct cell types interact and influence each other to build the foundation for the body. Until now it has been difficult to analyse these processes as they occur during the stages when the embryo is inaccessible, buried within the body of the mother. To gain insight into this developmental transition, we have established a culture system that, for the first time, permits manipulation and 4D-live imaging combined with computational analyses of embryos developing outside the mother continuously from fertilisation until future body plan emerges. This allows us to address how the pluripotent cells become endowed with the capability to develop into complex structures.
• Morris SA, Grewal S, Barrios F, Patankar SN, Strauss B, Buttery L, Alexander M, Shakesheff KM and Zernicka-Goetz M (2012) Dynamics of anterior-posterior axis formation in the developing mouse embryo. Nature Communications, 3:673.
• Ajduk A, Ilozue T, Windsor S, Yu Y, Seres KB, Bomphrey RJ, Tom BD, Swann K, Thomas A, Graham C and Zernicka-Goetz M (2011) Rhythmic actomyosin-driven contractions induced by sperm entry predict mammalian embryo viability. Nature Communications, 2, 417 doi:10.1038/ncomms1424
• Zernicka-Goetz M, Morris S and Bruce A (2009) Making a firm decision: layers of regulation in early mouse embryo. Nature Reviews Genetics, 10(7):467-77.
• Torres-Padilla ME, Parfitt DE, Kouzarides T and Zernicka-Goetz M (2007) Histone arginine methylation regulates pluripotency in the early mouse embryo. Nature, 445, 214-218