12 February 2003
Division over mammalian embryo cleavage
Developmental biologists at the Universities of Oxford and Cambridge are deeply divided on the issue of embryonic cell division. While a Cambridge group contend that the point at which a sperm penetrates the egg sets the pattern for subsequent embryonic cell division, Oxford researchers remain to be convinced.

The Cambridge group, which has been studying the orientation of the very first cleavage in mouse embryos, recently reported that the "sperm entry point" (SEP) has a role to play in setting up embryonic axes that direct what will become the top and the tail of the developing embryo.

But the Oxford group calls into question the methodology leading to such a conclusion. Richard Gardner, head of the University of Oxford's Mammalian Development Laboratory, is concerned that the idea that the SEP specifies the plane of first cleavage has already entered the lore of early mammalian development. "We would argue that it still lacks any incisive experimental support," he urged.

Resolution of this disagreement does not look imminent. Gardner's concerns about the methodology were recently published in Reproductive Biomedicine Online ( RBO). The Cambridge group, headed by Magdalena Zernicka-Goetz of the Wellcome Trust/Cancer Research UK Institute of Cancer and Developmental Biology, has countered each of Gardner's criticisms in a response also to be published in RBO.

In the last few years, it has emerged that the pattern of cell division in the early mammalian embryo is not entirely random as had been assumed, but that something intrinsic to the egg helps specify the line along which the first cleavage occurs.

In the course of research into what this something might be, Zernicka-Goetz says that her group "unexpectedly discovered that the SEP might also play a role in setting up early patterning."

This led Zernicka-Goetz to track the progress of the so-called fertilization cone, a transient structure that forms on the egg surface at the SEP. To do this, she labeled the structure with fluorescent beads that she says subsequently retain their relative position within the embryo. "We found an association of the label with the cleavage plane in 60% of embryos," she said, "a proportion that rose to 78% when we examined embryos actually in the process of cleavage."

But Gardner is far from convinced that beads are a reliable way of marking a point on the cell surface. "I tried the beads in 1997 to mark part of the surface of the zygote and, by means of various controls, found that they did not retain their location," he said. "Her controls ... are inadequate to justify the interpretation placed on them," he told BioMedNet News.

But Zernicka-Goetz accuses Gardner of "unfair distortion of the figures," and stands by her verification of the bead technique. She says that she and her co-author Karolina Piotrowska invited Gardner to visit her lab back in 2001 to witness their experiments first-hand. "Had they accepted our invitation, perhaps some of this public discussion could have been avoided," she told BioMedNet News.

Gardner remains unmoved. "Had Piotrowoska and Zernicka-Goetz performed adequate controls to convincingly show that in their hands the beads retained their ancestral position on the surface of the zygote, then it would have been appropriate for us to take up their offer to see their procedure," he said.

BioMedNet News
28 January 2003

Original web page at BioMedNet.