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This is a personal account of the discovery of the mesoderm-inducing activity of fibroblast growth factors. The background is my work on the dorsalising signal in early amphibian embryos that was done at the imperial Cancer Research Fund in London. I became interested in mesoderm induction because of the embryologic work of Nieuwkoop and the partial purification of a "vegetalising factor" by Tiedemann. Although, initially, we expected inducing factors to be novel substances, it gradually became clear that the impure preparations we were studying had properties in common with growth factors. This opened the way to the testing of candidate factors, resulting in the conclusion that some inducing factors and growth factors,in fact, were the same molecules despite being discovered through different routes and assayed using different methods. After a slow start looking at the molecular biology of fibroblast growth factors in Xenopus, we eventually found that their most interesting functions in early development lay not at the stage of mesoderm induction but, rather, in the anteroposterior patterning of the body, which occurs during gastrulation.

Homoeotic transformations are substitutions of one body part for another which arise during embryogenesis or regeneration. They are well known among the Arthropoda but are not generally thought to occur in Man or other vertebrates. In this paper the occurrence and characteristics of 21 types of epithelial heterotopia and metaplasia are reviewed and it is concluded that they are fully comparable with the homoeotic transformations of the arthropods.. The transformations are concentrated in the gastrointestinal, urinary and female reproductive systems and typically appear as foci of ectopic epithelium with a sharp discontinuity of cell type at the edges of the patches. Most of the transformations occur in renewal tissues and must therefore be interpreted as changes in the states of determination (epigenetic codings) of the stem cells rather than changes between already differentiated cells. Most, but not all, of the transformations are between tissues whose precursors are neighbouring regions of a common cell sheet during early embryogenesis and which are therefore likely to have neighbouring epigenetic codings. Following the Cairns hypothesis for epithelial organization it is proposed that stem cells themselves are protected against changes in epigenetic coding but their daughter cells, normally destined to differentiate and die, are not. Homoeotic transformations may thus occur in situations in which daughter cells become promoted to stem cells which happens either during the growth phase of the organism or during tissue regeneration in the adult.