Many of the genes that control the morphogenesis of the Drosophila embryo are evolutionarily related and share a similar 180 bp protein coding sequence called the homeo box. The homeo box protein domain contains a sequence-specific DNA binding activity, which suggests that homeo box genes might control development by regulating gene expression at the level of transcription. There are at least 30 homeo box genes in Drosophila, of which -20 have been cloned and characterized. Each of these genes shows a unique pattern of expression during early development. and is expressed in a characteristic subset of embryonic cells. Thus, virtually every cell contains a unique combination of active and inactive homeo box genes. It is thought that these different permutations of gene expression play an important role in selecting cell fate and specifying diverse patterns of morphogenesis. Abnormal patterns of homeo box gene expression can result in transformations of cell fate. thereby disrupting the spatial organization of the embryo. The long-range goal of the proposed research is to determine how selective patterns of homeo box gene expression are established during early development and neurogenesis. This study will include: (i) the localization of homeo box gene transcripts in maternal mutants that disrupt the early patterns of gap gene expression: (ii) the use of biochemical assays such as DNA binding and co-transfection of Drosophila tissue culture cells to examine regulatory interactions between the gap gene Kruppel and several pair-rule and homeotic genes: (iii) an evaluation of the in vivo significance of specific DNA sequences that have been shown to bind with high affinity to the homeo box protein even-skipped (eve) in vitro: and, (iv) the identification of "signal" sequences required for the sub-cellular localization of certain homeo box gene transcripts.