Early motivations

In 1977 we (L. M. A. and R. C. A.) submitted our first research proposal to the National Institutes of Health. The most speculative part was to use in situ hybridisation techniques to determine the distribution of individual mRNAs in sea urchin embryos. We suggested that information on spatial distribution would be useful in approaching three questions. First, we were puzzled that molecular assays of gene expression in whole embryos had led to the generalisation that most mRNAs are found throughout development (reviewed by Davidson, 1976, 1986) and that a relatively small percentage show large changes in abundance on a per embryo basis. The missing information required to interpret these observations was the extent to which genes are spatially regulated in different tissues or lineages. Second, we hoped to identify sets of mRNAs whose expression is co-ordinated in time and space, so that the mechanism of that co-ordination could be investigated. Third, we suggested that individual spatially restricted mRNAs could serve as molecular markers to construct a fate map of the embryo, to determine when cells commit to specific patterns of gene expression, and possibly to identify maternal RNAs localised in the egg. We proposed a longterm commitment to ‘localise the time and site of synthesis of individual mRNA species in developing embryos’. A dozen years seems an appropriately long time, and we take this opportunity to review the contribution of information gained from in situ hybridisation studies to the questions we initially anticipated, as well as to some we did not.