Mammalian chimaeras / Anne McLaren.

  • Anne McLaren
Date:
[1976]
Catalogue details
    142/168 page 132
    132 Perspectives tive than genetic similarity. The extreme of genetic divergence is provided by interspecific chimaeras. This is a field in which very little has so far been done, but which shows immense promise. In vitro, cells from species as re¬ mote as chick and mouse have been shown to co-operate morphogenetically, for example in the reconstruction of kidney tubules from dissociated cells. For interspecific studies, injection chimaeras are more suitable than aggre¬ gation chimaeras because the chimaerism is then limited to the embryo and is less likely to affect the interaction between trophoblast and uterus. The causes of interspecific hybrid breakdown (e.g. sheep x goat, Peromyscus maniculatus x P. polionotus) might be illuminated by combining the techniques of interspecies egg transfer and the injection of whole inner cell masses into trophoblast vesicles: the three variables of mother, trophoblast and embryo could in this way be varied independently. Sex chromosomes affect not only the direction of differentiation of the gonad and hence the individual, but also the development of the germ cells. Some interaction appears to take place between the sex chromosome con¬ stitution of the germ cells and the cellular environment in which they find themselves. For example, chimaera studies indicate that XX germ cells in a testis, in contrast to XY germ cells, enter meiosis before birth and fail to undergo spermatogenesis; but other lines of evidence have suggested that XO germ cells in a testis may be much more successful, even forming mature spermatozoa. Perhaps the requirement for normal germ cell development in the testis is absence of a second X chromosome rather than presence of a Y chromosome. Chimaeras made between XO and XY embryos should be able to confirm this hypothesis. There is also the intriguing case of the XY egg shed from the XX<^XY chimaeric ovary; did an initially XY germ cell succeed in undergoing oogenesis, only to suffer non-disjunction at the first meiotic division, or was the non-disjunctional event earlier, giving an XXY germ cell that survived in the ovary by virtue of its second X chromosome? If the second explanation is true, how do XO germ cells manage to differen¬ tiate into normal eggs? There is some evidence to indicate that the eggs developed from XO germ cells are not in fact normal (P. S. Burgoyne, per¬ sonal communication). The role of X and Y chromosomes in the develop¬ ment of germ cells as well as in sexual differentiation is an obvious target for chimaera studies. The factors determining susceptibility and resistance to tumours are of more than academic interest. In chimaeras between susceptible and resistant strains, the development of tumours seems often to be cell-autonomous, but by no means always. In chimaeras of at least one strain combination, lymphoma susceptibility is partially suppressed, despite the fact that most of the tissues contain an overwhelming majority of cells of the susceptible strain. How can so few resistant cells control such a large susceptible population? Perhaps some diffusible resistance-inducing substance exists. Again, why is it
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