Tissue Distribution of Gene Expression in Mammalian Development

The biochemical processes underlying development are ultimately dependent on accurately timed and regionally specific expression of particular genes. The latter fall into many categories, ranging from those specifying nuclear transcription factors through those coding for extracellular signaling molecules and their receptors to genes that determine structural and enzyme molecules that form the basis of morphology. Hybridization histochemistry has proved particularly valuable in defining at cellular levels the sites at which moderate or high concentrations of relevant mRNAs are to be found. The methods have been widely applied to delineating the areas of expression of control genes that define the “address” of cells as belonging to particular regions of the body (e.g., the Hox genes). There is also an extensive literature describing the use of in situ techniques in demonstrating the onset of transcription of genes coding for specific structural proteins, as well as for paracrine or endocrine secretions of hormones and growth factors important during development. Topographical delineation of message allows us to distinguish the cells in which functionally important peptides are synthesized from those on which they exert their physiological effect. Indeed, the additional demonstration of receptor mRNA often makes it possible to define cellular interactions in precise topographical terms, particularly when supportive immunocytochemical evidence of the relevant proteins is available. Besides their important use in monitoring normal developmental processes, techniques of hybridization histochemistry have been widely applied to investigating the expression of transcriptionally active transgenes and, in particular situations, to gain further insight into the phenomenon of imprinting.