In multicellular organisms the determination of anterior-posterior (A-P) embryonic poloarity is fundamental to subsequent development since the entire body plan is constructed relative to this axis. Little is known about the molecular mechanisms by which embryonic polarity is established and how axial information is transduced into cell fate. Genetic and molecular analyses have shown that many of the molecules that specify embryonic polarity and pattern are synthesized maternally in the ovarian follicies. Drosophila melanogaster is an excellent organism in which to pursue the mutational analysis of developmental phenomena to the molecular level and also possesses specific advantages for the study of oogenesis. This proposal aims to analyze genetically and molecularly four loci in Drosophila required during oogenesis for the formation of the anterior-posterior embryonic axis: torso (9 alleles), spliced (1 allele), exuperantia (4 alleles) and dicephalic (1 allele). Together, the mutant phenotypes of these four loci encompass the entire range of phenotypic abnormalities of the roughly twenty loci involved in establishing the A-P axis, and analyses of mutant combinations suggest that their gene products form part of an interacting system of molecules involved in specifying embryonic polarity. Genetic analysis will be used to characterize in detail existing and newly isolated alleles at these loci and to map them at high resolution cytogenetically. The molecular analyses will focus on the loci found to be most interesting genetically as well as most tractable molecularly. The structure of the transcripts, their spatial distribution and protein- coding potential will be determined. Homologies to known proteins may suggest functional, enzymatic roles for the encoded proteins. Subsequently, antisera will be raised against fusion proteins and used to analyze the spatial and temporal expression of the protein products of the cloned genes. The results of the spatial analyses of the gene products will have an important bearing on the general developmental and cell biological problem of how spatial asymmetries are established in cells, and will constrain possible molecular models of pattern formation. In the longer term, biochemical studies of the gene products and their activities and interactions, should provide mechanistic insights into one of the central processes in the development of multicellular organisms.
| Strecker, T R; Yip, M L; Lipshitz, H D (1992) Genetic control of cell fate in the termini of the Drosophila embryo. Dev Biol 150:422-6 |
| Lipshitz, H D (1991) Axis specification in the Drosophila embryo. Curr Opin Cell Biol 3:966-75 |
| Strecker, T R; Yip, M L; Lipshitz, H D (1991) Zygotic genes that mediate torso receptor tyrosine kinase functions in the Drosophila melanogaster embryo. Proc Natl Acad Sci U S A 88:5824-8 |
| Strecker, T R; Halsell, S R; Fisher, W W et al. (1989) Reciprocal effects of hyper- and hypoactivity mutations in the Drosophila pattern gene torso. Science 243:1062-6 |
