At the 18th conference of the European Teratology Society, held in Edinburgh in September 1990, several workshops were held.
The first concerned receptor targeting and development, and discussed how far experimental teratology has taken into consideration the highly sophisticated pharmacological nature of many compounds now being tested for their effects on the developing fetus. Compounds are now being developed with very specific receptor targets, high affinity for the receptor, and long duration of action. Toxicological techniques are not keeping pace. It is difficult to assess the effect of such highly specific compounds on the developing organism since they can affect the final receptor populations of whole pharmacological systems, and the critical period for alterations of function that result from such effects may extend well into post-natal life, as receptors continue to develop. The simple dose response curve (incidence of adverse effects increasing with increasing dose) does not necessarily apply with such selective receptor agonists/antagonists. In short, the sophistication of the compound may be greater than the methods used to detect adverse effects. It is concluded that more pharmacological awareness should be shown of the nature of the compound being tested, and consideration should be given to introducing receptor function tests in post-natal assessment.
In the second workshop, on gene expression in development, Professor Beck described some of the newer molecular techniques and how they can be applied to answer questions such as how the developing organism defines temporal and positional variables. The discovery of homeobox genes, first in Drosophila and subsequently throughout the animal kingdom, was a great step forward. Various techniques which allow the detection of changes in mRNA production can show which genes are active at a particular stage in development, though there are difficulties in studying very early stages of development as the yield of RNA is small from individual embryos. In situ hybridisation using oligonucleotide probes, in which the radio labelled probes are applied directly to different sections of an embryo, shows the timing and distribution of activity of relevant genes during development. Thus in the rat the IGFII gene is active from the 7th day of gestation, and is tissue specific, confined to the liver, the choroid plexus and the yolk sac. Cellular localisation of activity can be achieved using bright field microscopy. The technique of subtractive hybridisation allows detection of specific mRNA molecules that are produced at critical stages in development, and has been used to identify genes that are switched on at the gastrulation stage of Xenopus embryos.
The third workshop concerned pattern formation. The processes of cell determination, induction, specification and commitment are pathways whereby the cells of the embryo achieve their final differentiated state. Positional information, from which pattern is formed, is given by chemical gradients, for which cells have several distinct concentration-dependent differentiation responses. In the development of the axial skeleton the craniocaudal patterning of the somite segments can be altered by non-specific insult, and here the examination of homeobox complexes and their gene expression in somites following insults that alter axial patterning offers possibilities. An important component of pattern formation is the definition of laterality, so important in the development of non-midline organs and function. There are numerous unilateral malformations, eg of the limb and the cardiovascular system, in which laterality mechanisms are important factors. For the understanding of all these, the specific disruptions of pattern produced by chemical teratogens hold a key role, and their investigation at the molecular level will be highly profitable.
Participants in the first symposium included Dr M Feenstra, T Slotkin; in the second Professor F Beck and D Tweats; the third Dr S Wadden, O Wilby, N Brown; and in the opening symposium of the conference L Wolpert and M Goulding.