Small bristles, the Drosophila ortholog of NXF-1, is essential for mRNA export throughout development.

We identified a temperature-sensitive allele of small bristles (sbr), the Drosophila ortholog of human TAP/NXF-1 and yeast Mex67, in a screen for mutants defective in mRNA export. We show that sbr is essential for the nuclear export of all mRNAs tested in a wide range of tissues and times in development. High resolution and sensitive in situ hybridization detect the rapid accumulation of individual mRNA species in sbr mutant nuclei in particles that are distinct from nascent transcript foci and resemble wild-type export intermediates. The particles become more numerous and intense with increasing time at the restrictive temperature and are exported very rapidly after shifting back to the permissive temperature. The mRNA export block is not due indirectly to a defect in splicing, nuclear protein import, or aberrant nuclear ultrastructure, suggesting that in sbr mutants, mRNA is competent for export but fails to dock or translocate through NPCs. We conclude that NXF-1 is an essential ubiquitous export factor for all mRNAs throughout development in higher eukaryotes.

small bristles is required for the morphogenesis of multiple tissues during Drosophila development.

We found that mutations in small bristles (sbr) affect several tissues during the development of the fruit fly. In sbr embryos, neurons have defects in pathfinding and the body wall muscles have defective morphology. As adults, sbr flies have smaller and thinner bristles with a reduced diameter, suggesting a defective cytoskeleton within. The phenotypes we observe are consistent with defects in cell morphogenesis. We identified DmNXF1, the Drosophila homolog of a mRNA export protein that has been characterized in human (NXF1/TAP) and yeast (Mex67p) as the protein encoded by the small bristles locus. Given that a global decrease in mRNA export in these mutants is likely, the phenotypes we observe suggest that certain tissues are acutely sensitive to lower levels of cytoplasmic mRNA and the resultant decrease in protein synthesis during key stages of cellular morphogenesis.

From the growth cone surface to the cytoskeleton: one journey, many paths.

The mechanisms that guide axons through a complex cellular landscape to reach appropriate target cells are central to our understanding of neural development. Decades of work suggest that guidance information is interpreted by signaling machinery that controls the complex and dynamic cytoskeleton at the growth cone leading edge. Recent insights from the areas of signal transduction and cell biology have identified a number of key components that play central roles in this chain of command, including members of the Ena/VASP and WASP family of proteins. Although our understanding of the precise mechanism by which these proteins control actin assembly is still incomplete, these players are emerging as potential sites of integration that translate convergent signals into directional cell movement. This brief review explores some of the most recent articles on this topic.

The tyrosine kinase Abl and its substrate enabled collaborate with the receptor phosphatase Dlar to control motor axon guidance.

Genetic analysis of growth cone guidance choice points in Drosophila identified neuronal receptor protein tyrosine phosphatases (RPTPs) as key determinants of axon pathfinding behavior. We now demonstrate that the Drosophila Abl tyrosine kinase functions in the intersegmental nerve b (ISNb) motor choice point pathway as an antagonist of the RPTP Dlar. The function of Abl in this pathway is dependent on an intact catalytic domain. We also show that the Abl phosphoprotein substrate Enabled (Ena) is required for choice point navigation. Both Abl and Ena proteins associate with the Dlar cytoplasmic domain and serve as substrates for Dlar in vitro, suggesting that they play a direct role in the Dlar pathway. These data suggest that Dlar, Abl, and Ena define a phosphorylation state-dependent switch that controls growth cone behavior by transmitting signals at the cell surface to the actin cytoskeleton.

Rapid detection of group B streptococci directly from vaginal swabs.

Duplicate vaginal swabs were obtained from patients who attended obstetric or gynecologic clinics affiliated with the Magee Womens Hospital in Pittsburgh. One swab was cultured semiquantitatively on 5% sheep blood agar to detect group B streptococci (GBS). The other swab was subjected to a rapid method (25 min) for antigen detection and micronitrous acid exposure to extract the GBS antigen, followed by latex particle agglutination. A total of 464 swabs were evaluated by direct plating. Fifty-two swabs (11.2%) were found to contain GBS. Overall, the rapid method detected 21 of 52, or 40.4%, positive specimens. The sensitivity of the rapid method for identifying the most heavily colonized samples was 85.7%. This method can be used to identify maternity patients who are heavily colonized with GBS and are at high risk of delivering septic infants.