Settling a hotly debated issue in the field of cloning, a team of researchers from the Whitehead Institute and the University of Hawaii has shown that the egg can reset the developmental clock of a female adult cell, first reversing and then faithfully reproducing an early genetic event called X-inactivation. X-inactivation is a process by which one of two X chromosomes in female embryos is randomly silenced during development.

The findings, published in Fridays issue of Science, provide the first molecular evidence for the eggs ability to reprogram an adult cell back to its embryonic state and show for the first time that the process of X-inactivation in clones occurs in a manner similar to that in normal development.

Since Dolly was first cloned, researchers have debated whether she has random X-inactivation as normal females do or the same X chromosome inactivated in all her cells (the X that was inactive in the mammary cell nucleus from which she had been cloned). In this study, scientists from Rudolf Jaenischs laboratory at the Whitehead Institute and Ryuzo Yanagimachis laboratory at the University of Hawaii used their expertise in cloning mice to answer this question. Their results show that X-inactivation is random in the cells of cloned animals. The egg therefore is able to reprogram the X chromosome of an adult cell to a state that is appropriate for an embryonic one.

"Scientists have suggested that cloning of mammals by nuclear transfer requires reprogramming of the differentiated state of donor cell to an embryonic ground state, but there was no direct molecular evidence for such reprogramming. The process of X-inactivation is an example. It has never been clear whether this process is reversible during cloning," says Jaenisch. Cloning is a very inefficient process, and it is possible that faulty reprogramming contributes to the low success rate. "It will therefore be crucial to determine whether the expression state of other genes
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Contact: Nadia Halim
halim@wi.mit.edu
617-258-9183
Whitehead Institute for Biomedical Research
22-Nov-2000