Faculty Bibliography

RNA interference (RNAi) has been shown to spread from cell to cell in plants and in Caenorhabditis elegans, but it does not spread in other organisms, such as Drosophila. A recent report demonstrates that a membrane channel, encoded by the gene sid-1, is responsible for the spreading of RNAi between cells.

Cell fate diversity can be achieved through the asymmetric segregation of cell fate determinants. In the Drosophila embryo, neuroblasts divide asymmetrically and in a stem cell fashion. The determinants Prospero and Numb localize in a basal crescent and are partitioned from neuroblasts to their daughters (GMCs). Here we show that nonmuscle myosin II regulates asymmetric cell division by an unexpected mechanism, excluding determinants from the apical cortex. Myosin II is activated by Rho kinase and restricted to the apical cortex by the tumor suppressor Lethal (2) giant larvae. During prophase and metaphase, myosin II prevents determinants from localizing apically. At anaphase and telophase, myosin II moves to the cleavage furrow and appears to "push" rather than carry determinants into the GMC. Therefore, the movement of myosin II to the contractile ring not only initiates cytokinesis but also completes the partitioning of cell fate determinants from the neuroblast to its daughter.

Regulation of stem cell division is of particular interest, both for studies of development and for stem cell therapeutics. In this issue of Neuron, Bello et al. show that the number of divisions of Drosophila neural stem cells is limited, in a region-specific manner, by regulated apoptosis in response to a pulse of expression of the Hox gene abdominal-A (abdA).

BACKGROUND:The cytoskeleton and associated motors play an important role in the establishment of intracellular polarity. Microtubule-based transport is required in many cell types for the asymmetric localization of mRNAs and organelles. A striking example is the Drosophila oocyte, where microtubule-dependent processes govern the asymmetric positioning of the nucleus and the localization to distinct cortical domains of mRNAs that function as cytoplasmic determinants. A conserved machinery for mRNA localization and nuclear positioning involving cytoplasmic Dynein has been postulated; however, the precise role of plus- and minus end-directed microtubule-based transport in axis formation is not yet understood. RESULTS:Here, we show that mRNA localization and nuclear positioning at mid-oogenesis depend on two motor proteins, cytoplasmic Dynein and Kinesin I. Both of these microtubule motors cooperate in the polar transport of bicoid and gurken mRNAs to their respective cortical domains. In contrast, Kinesin I-mediated transport of oskar to the posterior pole appears to be independent of Dynein. Beside their roles in RNA transport, both motors are involved in nuclear positioning and in exocytosis of Gurken protein. Dynein-Dynactin complexes accumulate at two sites within the oocyte: around the nucleus in a microtubule-independent manner and at the posterior pole through Kinesin-mediated transport. CONCLUSION/CONCLUSIONS:The microtubule motors cytoplasmic Dynein and Kinesin I, by driving transport to opposing microtubule ends, function in concert to establish intracellular polarity within the Drosophila oocyte. Furthermore, Kinesin-dependent localization of Dynein suggests that both motors are components of the same complex and therefore might cooperate in recycling each other to the opposite microtubule pole.

Ephrin/Eph signalling is crucial for axonal pathfinding in vertebrates and invertebrates. We identified the Drosophila ephrin orthologue, Dephrin, and describe for the first time the role of ephrin/Eph signalling in the embryonic central nervous system (CNS). Dephrin is a transmembrane ephrin with a unique N terminus and an ephrinB-like cytoplasmic tail. Dephrin binds and interacts with DEph, the Drosophila Eph-like receptor, and Dephrin and DEph are confined to different neuronal compartments. Loss of Dephrin or DEph causes the abberant exit of interneuronal axons from the CNS, whereas ectopic expression of Dephrin halts axonal growth. We propose that the longitudinal tracts in the Drosophila CNS are moulded by a repulsive outer border of Dephrin expression.

Asymmetric cell division can produce daughter cells with different developmental fates and is often accompanied by a difference in cell size. A number of recent genetic and in vivo imaging studies in Drosophila and Caenorhabditis elegans have begun to elucidate the mechanisms underlying the rearrangements of the cytoskeleton that result in eccentrically positioned cleavage planes. As a result, we are starting to gain an insight into the complex nature of the signals controlling cytoskeletal dynamics in the dividing cell. In this commentary we discuss recent findings on how the mitotic spindle is positioned and on cleavage site induction and place them in the context of cell size asymmetry in different model organisms.

Since its introduction into heterologous organisms as a marker of gene expression, the green fluorescent protein (GFP) has led a dramatic revolution in cell, developmental and neurobiology. By allowing breathtaking visualization of fluorescent fusion proteins as they move within and between cells, GFP has fundamentally transformed the spatial analysis of protein function. Now, new GFP technologies allow far more than simple observations of fusion protein localization. The growing family of fluorescent protein variants is enabling more sophisticated studies of protein function and illuminating wide-ranging processes from gene expression to second-messenger cascades and intercellular signalling. Together with advances in microscopy, new GFP-based experimental approaches are forging a second GFP revolution.

Cell-fate diversity is generated in part by the unequal segregation of cell-fate determinants during asymmetric cell divisions. In the Drosophila pupa, the pI sense organ precursor cell is polarized along the anterior-posterior axis of the fly and divides asymmetrically to generate a posterior pIIa cell and an anterior pIIb cell. The anterior pIIb cell specifically inherits the determinant Numb and the adaptor protein Partner of Numb (Pon). By labelling both the Pon crescent and the microtubules in living pupae, we show that determinants localize at the anterior cortex before mitotic-spindle formation, and that the spindle forms with random orientation and rotates to line up with the Pon crescent. By imaging living frizzled (fz) mutant pupae we show that Fz regulates the orientation of the polarity axis of pI, the initiation of spindle rotation and the unequal partitioning of determinants. We conclude that Fz participates in establishing the polarity of pI.