The generation of distinct cell fates during development depends on asymmetric cell division of progenitor cells. In the central and peripheral nervous system of progenitor cells respectively called neuroblasts or sensory organ precursors use PAR polarity during mitosis to control cell fate determination in their daughter cells. How polarity and the cell cycle are coupled, and how the cell cycle machinery regulates PAR protein function and cell fate determination is poorly understood.
View Article and Find Full Text PDFA functional centrosome is vital for the development and physiology of animals. Among numerous regulatory mechanisms of the centrosome, ubiquitin-mediated proteolysis is known to be critical for the precise regulation of centriole duplication. However, its significance beyond centrosome copy number control remains unclear.
View Article and Find Full Text PDFApical-basal polarity is an essential epithelial trait controlled by the evolutionarily conserved PAR-aPKC polarity network. Dysregulation of polarity proteins disrupts tissue organization during development and in disease, but the underlying mechanisms are unclear due to the broad implications of polarity loss. Here, we uncover how Drosophila aPKC maintains epithelial architecture by directly observing tissue disorganization after fast optogenetic inactivation in living adult flies and ovaries cultured ex vivo.
View Article and Find Full Text PDFDrosophila is an important model system to study a vast range of biological questions. Various organs and tissues from different developmental stages of the fly such as imaginal discs, the larval brain or egg chambers of adult females or the adult intestine can be extracted and kept in culture for imaging with time-lapse microscopy, providing valuable insights into cell and developmental biology. Here, we describe in detail our current protocol for the dissection of Drosophila larval brains, and then present our current approach for immobilizing and orienting larval brains and other tissues on a glass coverslip using Fibrin clots.
View Article and Find Full Text PDFAsymmetric cell division (ACD) is the fundamental process through which one cell divides into two cells with different fates. In animals, it is crucial for the generation of cell-type diversity and for stem cells, which use ACD both to self-renew and produce one differentiating daughter cell. One of the most prominent model systems of ACD, Drosophila neuroblasts, relies on the PAR complex, a conserved set of proteins governing cell polarity in animals.
View Article and Find Full Text PDF() is the most frequently mutated gene in colorectal cancer. APC negatively regulates the Wnt signaling pathway by promoting the degradation of β-catenin, but the extent to which APC exerts Wnt/β-catenin-independent tumor-suppressive activity is unclear. To identify interaction partners and β-catenin-independent targets of endogenous, full-length APC, we applied label-free and multiplexed tandem mass tag-based mass spectrometry.
View Article and Find Full Text PDFStudying the function of proteins using genetics in cycling cells is complicated by the fact that there is often a delay between gene inactivation and the time point of phenotypic analysis. This is particularly true when studying kinases that have pleiotropic functions and multiple substrates. neuroblasts (NBs) are rapidly dividing stem cells and an important model system for the study of cell polarity.
View Article and Find Full Text PDFControlling the orientation of cell division is important in the context of cell fate choices and tissue morphogenesis. However, the mechanisms providing the required positional information remain incompletely understood. Here we use stem cells of the Drosophila larval brain that stably maintain their axis of polarity and division between cell cycles to identify cues that orient cell division.
View Article and Find Full Text PDFCell fate assignment in the nervous system of vertebrates and invertebrates often hinges on the unequal distribution of molecules during progenitor cell division. We address asymmetric fate determinant localization in the developing nervous system, specifically the control of the polarized distribution of the cell fate adapter protein Miranda. We reveal a step-wise polarization of Miranda in larval neuroblasts and find that Miranda's dynamics and cortical association are differently regulated between interphase and mitosis.
View Article and Find Full Text PDFIntercellular bridges called "ring canals" (RCs) resulting from incomplete cytokinesis play an essential role in intercellular communication in somatic and germinal tissues. During Drosophila oogenesis, RCs connect the maturing oocyte to nurse cells supporting its growth. Despite numerous genetic screens aimed at identifying genes involved in RC biogenesis and maturation, how RCs anchor to the plasma membrane (PM) throughout development remains unexplained.
View Article and Find Full Text PDFHow adhesive contacts with neighbors may affect epithelial cell cytokinesis is unknown. We report that in Drosophila, septins are specifically required for planar (but not orthogonal) cytokinesis. During planar division, cytokinetic furrowing initiates basally, resulting in a contractile ring displaced toward the adherens junction (AJ).
View Article and Find Full Text PDFThe Notch signaling pathway regulates numerous aspects of metazoan development and tissue renewal. Deregulation or loss of Notch signaling is associated with a wide range of human disorders from developmental syndromes to cancer. Notch receptors and their ligands are widely expressed throughout development, yet Notch activation is robustly controlled in a spatio-temporal manner.
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