It is a vital and formative stage of early embryo development, but scientists have long struggled to understand what happens in the weeks after conception and before organs begin to form and mature in the womb.
Now, in what is the first detailed cellular and molecular examination of its kind, described as a “Rosetta stone” for modern biology, new light has been shed on the human embryo as it undergoes a process known as gastrulation.
Experts say gastrulation is one of the most critical steps of development, and takes place roughly between days 14 and 21 after fertilisation.
During this period, the embryo transforms from a one-dimensional layer of cells and reorganises into a multi-layered and multidimensional structure called the gastrula.
Analysing a single embryo, scientists from Oxford University and the Helmholtz Zentrum Munchen, in Germany, identified 11 distinct cell types, including red blood cells and primordial cell germs, which provide the foundations for the later production of egg and sperm cells.
The researchers also found that the nervous system had not yet begun to take shape at this stage of development.
Principal study investigator Professor Shankar Srinivas, from Oxford University, said: “Our body is made up of hundreds of types of cells.
“It is at this stage that the foundation is laid for generating the huge variety of cells in our body – it’s like an explosion of diversity of cell types.”
Scientists say the study, published in Nature, is a milestone for developmental biology as ethically acquired human samples at these early stages are exceptionally rare.
The sample was obtained through the Human Developmental Biology Resource, from an anonymous donor who provided consent for researchers to use embryonic material arising from the termination of her pregnancy.
The sample is estimated to be from around 16 to 19 days after fertilisation.
Lead researcher Dr Richard Tyser said: “This is such an early stage of development that many people would not have known they were pregnant.
“It is the first time an embryo at this stage of development has been characterised in such detail using modern technology.”
Legally, scientists are only able to grow human embryos in a lab up to the equivalent of 14 days of development – just before the start of gastrulation.
Therefore the knowledge of events beyond 14 days after fertilisation is largely based on studies in animals, such as mice and chickens.
Dr Tyser said: “Our new sample is the bridge that links the very early stage of development with the later stages when organs begin to form.
“This link in the human had previously been a black box, so we had to rely on other model organisms such as the mouse.
“Reassuringly, we have now been able to show that the mouse does model how a human develops at the molecular level.
“Such models were already providing valuable insights, but now this research can be further enriched by the fact we’re able to cast light into that black box and more closely see how it works in humans.”
Speaking at a press briefing, Prof Srinivas said researchers did not see any neurons in the sample.
“We didn’t see any differentiated neurons to the sample, which tells us that the human embryos at this earlier stage are not equipped to sense their environment in many ways, and certainly can’t by any stretch of the imagination be said to be have any mechanism for consciousness for example – the cells just aren’t there.”
Scientists believe the findings of the study could help to further understanding of miscarriages and congenital abnormalities, which are thought to be driven by complications that emerge during the gastrulation stage of early development.
“The new study provides a Rosetta Stone for developmental biologists,” said Dr Peter Rugg-Gunn, of the Babraham Institute at the University of Cambridge. “The new study is already yielding important new insights into how the early cell lineages are formed and positioned in the developing embryo.
“This information provides new leads to understand why these processes sometimes go wrong during pregnancy, which can result in developmental defects in some babies.”
Darren Griffin, a professor of genetics at the University of Kent, said: “It is a landmark paper, upon which many will base their future findings.”