How Embryo Aligns "Head to Tail" Now Visable
Scientists can now view critical head formation of mammalian embryo using a gene that "glows"
For several decades it has been possible to culture embryos from a single cell, the fertilized egg, into the blastocyst - a ball of some 64 cells all derived from the first cell division. In practical terms this has allowed the development of the in vitro fertilization techniques used world-wide to assist fertility.
Culturing embryos has enabled scientists to learn a lot about early development. This is because in the first 4 days it is possible to observe events as they happen and, in model systems such as the mouse, manipulate the expression of the genes during those 4 days in order to better define the role each plays.
The 64 cells of the blastocyst make up three cell types, a small number of stem cells that will develop into the future body, cradled within two extra-embryonic cell types that will contribute to the placenta - but will also signal developmental events as the stem cell population expands.
Currently, there is a good understanding of the molecular and cellular events resulting in the formation of these three cell types.
In contrast, scientists' knowledge of subsequent events has been extremely restricted. Around the fourth day the developing embryo implants into the uterine wall, becoming hidden from view. Yet this is a very important phase of development as now extra-embryonic tissues signal stem cells where to start making the head and rear of the body.
A novel approach in the study of development of mammalian embryos was reported (14 February) in the journal Nature Communications. The research, from the laboratory of Professor Magdalena Zernicka-Goetz of the University of Cambridge, enables scientists to view critical aspects of embryo growth previously unobservable.
Typically, researchers recover embryos from model systems - such as the mouse - and build up a picture of what is happening. Until now, however, it has been impossible to record the process of body orientation as it is happening, let alone carry out experiments to understand all the processes involved.
Using the mouse embryo model, Professor Zernicka-Goetz and her colleagues, with funding from the Wellcome Trust, have developed a method allowing them to overcome the barrier of implantation by culturing and imaging embryos outside the body of the mother for the first 8 days of development.
More importantly, the movies that Professor Zernicka-Goetz' team now make of this critical period are revealing secrets: the origins of extra-embryonic cell clusters that signal where to make the head of the embryo. They can now track these cells using a gene marked by a protein (that glows) and expressed only in the "head" signaling region, of living mouse embryos in culture.
In this way they determined that the "head" cell clusters originate from one or two cells at the blastocyst stage whose daughter cells will ultimately cluster into a specific region of the embryo before migrating to a final position and signaling further head development. The cells that lead this migration play an important role and need to be understood.
Dr. Zernicka-Goetz: "Not only is this approach uncovering events previously hidden from view, but it has other important potential applications. This is the period of development during which the natural population of stem cells undergoes expansion to form the foundation upon which the body can be built.
In the mouse it is fairly easy to establish stem cell lines from embryos at the blastocyst stage that have the capability of contributing to all body tissues and indeed from which an entire new organism can be built. In humans, however, such lines are more difficult to establish. The new technique offers hope that by permitting the expansion of the natural stem cell population in a manner that resembles normal development, it should make establishing stem cell lines much easier.
What is certain is that it will allow direct experimental access to this stage of development and should therefore provide the means of gaining greater understanding of embryonic stem cells in their natural development."
Work was carried out in the Gurdon Institute, University of Cambridge and the culture substrates were developed in collaboration with a School of Pharmacology in Nottingham.
The paper 'Dynamics of anteriorposterior axis formation in the developing mouse embryo' will be published in the 14 February 2012 edition of Nature Communications.
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Original article: http://www.cam.ac.uk/research/news/critical-stage-of-embryonic-development-now-observable/