Cytoskeletal Regulation During Embryonic Development in Drosophila melanogaster

Sammanfattning: The development of multicellular organisms is associated with extensive rearrangements of cells and tissues. The driving force for these rearrangements is generated by the cell's actin cytoskeleton. During many morphogenetic processes dynamic rearrangement of the actin cytoskeleton is regulated by small GTPases of the Rho-family. These GTPases are highly conserved throughout the animal kingdom and act as bipolar molecular switches that are activated by guanine nucleotide exchange factors (GEFs). The broad tissue distribution of Rho-family GTPases and the presence of a large number of RhoGEFs in the genome have led to the hypothesis that specific aspects of Rho-function might be regulated by specific RhoGEFs in a tissue-specific manner. DRhoGEF2, which is the Drosophila ortholog of the human RGS-domain-containing RhoGEFs, PDZ-RhoGEF, Leukemia associated RhoGEF (LARG) and P115 RhoGEF, has previously been shown to regulate the coordinated cell shape changes that drive the invagination of mesodermal and endodermal germlayers during gastrulation. The tissue distribution of DRhoGEF2 protein suggested a requirement of DRhoGEF2 in a broad range of tissues during embryonic development. This thesis describes the role of DRhoGEF2 during early embryonic development in processes such as metaphase furrow formation, pole cell formation and blastoderm cellularization as well as its later function in the formation of segmental grooves. All processes requiring DRhoGEF2 function involve the contraction of Actin-Myosin fibers and together with previous studies the presented results suggest that DRhoGEF2 regulates the activity of the small GTPase Rho1 during morphogenetic movements that require the contractile activity of actomyosin networks.