Vida humana

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Your destiny, from day one
The mammalian body plan starts being laid down from the moment of conception, it has emerged. Helen Pearson considers the implications of a surprising shift in embryological thinking.
Axes established in the two-celled embryo (left in this montage) set up those in the fetus.

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our world was shaped in thefirst 24 hours after conception. Where your head and feet would sprout, and which side would form your back and which your belly, were being defined in the minutes and hours after sperm and egg united. Just five years ago, this statement would have been heresy. Mammalian embryos were thought to spend their first few days as a featureless orb of cells. Only later, at about the time of implantationinto the wall of the uterus, were cells thought to acquire distinct ‘fates’ determining their positions in the future body. But by tagging specific points on mammalian eggs shortly after fertilization, researchers have now shown that they come to lie at predictable points in the embryo. Rather than being a naive sphere, it seems that a newly fertilized egg has a defined top–bottom axis that setsup the equivalent axis in the future embryo. Controversially, one group even claims that the spot on the egg at which the sperm enters determines where the first cell division occurs — and that the resulting two cells already have a bias towards different fates. This new understanding opens fresh avenues of study for developmental biologists. But it also raises the possibility that any techniquethat meddles with early human development — such as the removal of cells from an early embryo for pre-implantation genetic testing — might potentially be harmful.“It’s possible you could be removing a cell with a predictable fate and causing damage,” says Alan Handyside, who studies embryo abnormalities at the University of Leeds,UK. Biologists have long known that the eventual axes of the embryoin most species are laid down either before fertilization, or in the first hours afterwards. In fruit flies, for

instance, the egg inherits a molecule that is more concentrated at one end of the egg than the other, and thus defines the head–tail axis. Heads or tails? But mammalian embryos were considered to be a special case. First, they have a striking ability to compensate for damage. Split upthe first two cells of a mouse embryo and both recover to make two apparently normal mice. Second, only around 15% of cells in the blastocyst — a hollow sphere of cells that forms some five days after conception — contribute towards the body proper, rather than supporting tissues such as the placenta. These cells reside in a structure called the inner cell mass (ICM). Finally, the first visiblesign of a distinguishable head or tail takes 6.5 days to appear in mouse embryos. “All that argued against the idea of there being a map on the egg,” says developmental biologist John Gurdon of the Wellcome/ Cancer Research UK Institute of Cancer and
This way up: Richard Gardner injected oil drops into two-celled embryos (below), giving markers that showed up in the blastocyst (below right).Developmental Biology in Cambridge. The first hint that the blastocyst was not the unassuming orb it appeared came in the 1980s. Two little-noticed studies from Jean Smith of Queen’s College in Flushing, New York, showed that the mouse blastocyst, rather than a being a symmetrical sphere, is slightly distorted and has recognizable axes1,2. What’s more, these axes appeared to match up with those ofthe fetus, suggesting that the former sets up the latter. The findings prompted Richard Gardner, an embryologist at the University of Oxford, UK, to repeat the work, drawing similar conclusions3. But it took another five years before Gardner could make

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© 2002 Nature Publishing Group

| wwwNATURE | VOL 418 | 4 JULY 2002 | www.nature.com/nature

R. GARDNER

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