The embryonic expression pattern of 40 murine cDNAs homologous to Drosophila mutant genes (Dres): a comparative and topographic approach to predict gene function

Nature often utilizes the same metabolic 'core groups' of interacting genes or 'pathways' in completely different organs, tissues and cellular compart ments. Deciphering the physiological role of a particular gene in a living organism is therefore critical to understanding not only how a gene/protein works, but also where (in which tissue/organ) and when (at what developmen tal stage) it functions. We have performed systematic RNA in situ hybridiza tion on a subset of murine genes homologous to Drosophila mutant genes, cal led Drosophila-related expressed sequences (Dres), This approach combines f unctional information derived from cross-species sequence comparisons and b iochemical, physiological and pathological studies performed in the fly wit h knowledge of the spatial and temporal distribution of gene expression. Fo rty murine Dres were tested by RNA in situ hybridization on sagittal, coron al and transverse sections at three developmental stages, E10.5, E12.5 and E17.5. For some of them, whole mount in situ hybridization was performed at earlier stages. These data are valuable for establishing how the function of these genes and the genetic programs underlying the development of a par ticular tissue or organ have evolved during evolution, For example, six Dre s genes showed restricted expression domains within the murine! retina, sug gesting a different role for each of these genes in eye development and fun ctioning. Furthermore, the information derived from this combined approach will be instrumental in predicting the phenotypic consequences of gene dysf unction in both mouse mutants and human genetic diseases.