How does a single fertilized egg become a mammal? Two independent teams have now answered that question in far more detail, using gene-edited 'barcodes' to follow the cell divisions of mouse embryos. Their papers appeared on Thursday in Science and in Cell, as Nature reports.
The team led by Jay Shendure at the University of Washington used a technique they call DNA Typewriter, which adds sequential, indelible genetic marks to specific spots in the genome as cells divide. The fertilized egg was implanted into a mouse; after two weeks, when the embryo had formed major organ systems, the researchers read the edits back and reconstructed the relationships of about 1.3 million edited cells — roughly 10% of the embryo's total. A second team, led by Jonathan Weissman at the Whitehead Institute in Cambridge, Massachusetts, used a more precise and less damaging technique called prime editing to capture most cell divisions as organs formed.
Both studies were inspired by a landmark early-1980s effort: UK biologist John Sulston watched every cell of the nematode Caenorhabditis elegans as it grew from an egg into an adult with exactly 959 somatic cells — still the only complete map of an animal's development. Mammals are far harder. Their development is hidden, their cells number in the billions, and external cues such as growth factors decide whether a cell ends up in the lungs or the liver.
That is precisely the scientific puzzle: how do very different sets of cell divisions give rise to individuals of the same species with broadly the same form? 'Twins look the same, humans kind of look the same, yet even twins develop through very different sets of cell divisions,' Shendure said. Earlier CRISPR-based lineage recorders could damage cells if too many edits accumulated; the switch to prime editing was what made the mammalian maps possible. The result is a new kind of instrument for developmental biology — a way to ask, at the scale of an entire embryo, how bodies reliably build themselves.
