Homoeotic transformations in man: Implications for the mechanism of embryonic development and for the organization of epithelia

Abstract

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.