Pioneering work by a leading University of Nottingham scientist has helped reveal for the first time a vital process in the development of the early mammalian embryo.
A team led by Professor of Tissue Engineering, Kevin Shakesheff, has created a new device in the form of a soft polymer bowl which mimics the soft tissue of the mammalian uterus in which the embryo implants. The research has been published in the journal Nature Communications.
This new laboratory culture method has allowed scientists to see critical aspects of embryonic development that have never been seen in this way before. For the first time it has been possible to grow embryos outside the body of the mother, using a mouse model, for just long enough to observe in real time processes of growth during a crucial stage between the fourth and eighth days of development.
Professor Shakesheff said: “Using our unique materials and techniques we have been able to give our research colleagues a previously unseen view of the incredible behaviour of cells at this vital stage of an embryo’s development. We hope this work will unlock further secrets which could improve medical treatments that require tissues to regenerate and also open up more opportunities to improve IVF. In the future we hope to develop more technologies which will allow developmental biologists to understand how our tissue forms.”
In the past it has only been possible to culture a fertilised egg for four days as it grows from a single cell into a blastocyst, a ball of 64 cells comprising stem cells which will form the body, and extra-embryonic cells which form the placenta and control stem cell development as the embryo develops. But scientists’ knowledge of events at a cellular level after four days, when, to survive, the blastocyst has to implant into the mother’s womb, has up to now been limited. Scientists have had to rely on snap shots taken from embryos removed from the living uterus at different stages of development.
Now, thanks to The University of Nottingham team’s newly developed culture environment, scientists at Cambridge University have been able to observe and record new aspects of the development of the embryo after four days. Most importantly they have been able to see at first hand the process which is the first step in the formation of the head, involving pioneer cells moving a large distance (for a cell) within the embryo. They have observed clusters of extra-embryonic cells which signal where the head of the embryo should form. To track these cells in mouse embryos they have used a gene expressed only in this ‘head’ signalling region marked by a protein which glows.
In this way they have been able to work out that these cells come from one or two cells at the blastocyst stage whose progeny ultimately cluster together in a specific part of the embryo, before collectively migrating to the position at which they signal head development. The cells that lead this migration appear to have an important role in leading the rest and acting as pioneers.
This new breakthrough is part of a major research effort at Nottingham to learn how the development of the embryo can teach us how to repair the adult body. The work is led by Professor Kevin Shakesheff with prestigious funding from European Research Council.
Professor Shakesheff added: “Everyone reading this article grew themselves from a single cell. With weeks of the embryo forming all of the major tissues and organs are formed and starting to function. If we could harness this remarkable ability of the human body to self-form then we could design new medical treatments that cure diseases that are currently untreatable. For example, diseases and defects of the heart could be reversed if we could recreate the process by which cardiac muscle forms and gets wired into the blood and nervous system.”
Professor Shakesheff’s work was carried out in collaboration with scientists led by Professor Magdalena Zernicka-Goetz at the Gurdon Institute, Cambridge University.