Characterizing the role of Drosophila melanogaster ik2, an I -kappa -B kinase, in anterior -posterior and dorsal -ventral embryonic patterning

The intracellular localization of mRNAs is a conserved mechanism that polarized cells use to target proteins to the particular cellular regions where they are required. In Drosophila melanogaster, the embryonic body axes are established by the localization of maternal mRNAs in the oocyte. Both the anterior and posterior ends of the embryo are specified by the localization of bicoid mRNA and oskar mRNA, respectively, during oogenesis. In addition, the initial dorsal-ventral asymmetry depends on localization of gurken mRNA. The transport and maintenance of these mRNAs within the oocyte requires cytoskeletal elements.;In this dissertation, I have described the characterization of ik2, which encodes a member of the IkappaB kinase (IKK) family of protein serine/threonine kinases. In both Drosophila and mammalian immunity, IKKs regulate the activity of Rel/NF-kappaB transcription factors by targeting their inhibitory partner proteins, IkappaBs, for degradation. Members of a distinct family of IKK-like kinases are activated in response to viral infection, although the kinase substrates are interferon regulatory factors, and not Rel/NF-kappaB proteins. I have found that ik2 is homologous to the class of IKK-like kinases, and regulates the localization of maternal mRNAs during oogenesis in an NF-kappaB-independent manner.;I identified mutations in the ik2 kinase domain that cause recessive lethality. ik2 mutant females produce embryos that are both ventralized and bicaudal, with a duplicated abdomen in place of the head. Since the loss of function of ik2 affects both the anterior-posterior and dorsal-ventral embryonic axes, I analyzed the asymmetric distribution of maternal determinants in the oocyte. ik2 is required for proper localization of bicoid, oskar, and gurken mRNAs during oogenesis. In addition, I identified ectopic sites of actin polymerization within the oocyte, and global defects in the localization of microtubule minus ends within the oocyte. ik2 adult escapers also have abnormal interommatidial and thoracic bristles, which are actin-based structures. These data suggest that ik2 regulates an actin-based process that is required to organize the cytoskeleton and properly localize mRNAs within the oocyte.