A Morphologic Approach to Understanding Molecular Events During Development

Abstract

Through the combined technologies ofin situhybridization and transgenic mouse analysis major advances have been made in the understanding of developmental biology. Recent advances in understanding embryogenesis have been accomplished by determining specific gene activation during development, determining the cell specificity of individual activated genes, characterizing the cis regulatory elements of the developmentally regulated genes, and disrupting the activity and functions of these genes during critical stages of development through targeted mutation.In situhybridization provides highly specific and sensitive detailed information of both the spatial and temporal pattern of endogenous gene expression during embryogenesis. The regulatory elements that determine the tissue specific and temporal related expression pattern of these embryonic genes are then identified and characterized byin situhybridization through the generation of transgenic mice which carry gene constructs with reporter genes, such as CAT, luciferase, or lac Z, linked to the flanking DNA sequences that exert either positive or negative influence over the expression of the gene in question. Finally once the expression patterns and regulatory elements have been characterized targeted ablation of the developmentally regulated gene can determine or provide important insight into function.