Howard Hughes Medical Institute, Stanford University School of Medicine, California
A developmental biologist muses on the magic of the egg.
Many biologists, myself included, grew up watching frogs’ eggs hatch into tadpoles at the warm surfaces of summer ponds. The yearly cycle provided a leisurely period of thought about basic biology. But few of us guessed how central to current biological and financial interests the egg would become. These days, an enucleated egg’s ability to reprogram the nucleus of a somatic cell — first demonstrated in frogs’ eggs in 1958 — promises an era in which organs could be picked up like junkyard parts.
What magic does the egg possess that allows it to reset the nucleus to a basal, or ‘pluripotent’, state from which all cells can be generated? The three famous transcription factors — Oct4, Sox2 and Klf4 — that are required to transform a skin cell into a pluripotent cell provide some insight. But do these recapitulate a pattern used by the egg during development, or induce reprogramming by an alternative pathway?
John Gurdon and his colleagues at the Gurdon Institute in Cambridge, UK, have purified the proteins that bind to the regulatory sequences of the Oct4 gene in frogs’ eggs (M. J. Koziol et al. Curr. Biol. 17, 801–807; 2007). The group chose Oct4 because its regulatory regions have been clearly defined. They found that the initiation of Oct4 expression involved, in addition to likely candidates, some unexpected proteins.
If, as many scientists think is the case, the re-establishment of pluripotency involves shortcircuiting egg development, this suggests to me that the magic that allows the egg to reset a nucleus into a pluripotent state may lie in these unexpected proteins — as well as Oct4, Sox2 and Klf4. There is so much more to learn from watching frogs’ eggs grow up.