We have cloned and molecularly characterized the Drosophila gene stripe (sr) required for muscle‐pattern formation in the embryo. Through differential splicing, sr encodes two nuclear protein variants which contain a zinc finger DNA‐binding domain in common with the early growth response (egr) family of vertebrate transcription factors. The sr transcripts and their protein products are exclusively expressed in the epidermal muscle attachment cells and their ectodermal precursors, but not in muscles or muscle precursors. The results suggest that sr activity induces a subset of ectodermal cells to develop into muscle attachment sites and to provide spatial cues necessary to orient myotubes along the basal surface of the epidermis to their targeted attachment cells.

Small GTPases of the Rab family not only regulate target recognition in membrane traffic but also control other cellular functions such as cytoskeletal transport and autophagy. Here we show that Rab26 is specifically associated with clusters of synaptic vesicles in neurites. Overexpression of active but not of GDP-preferring Rab26 enhances vesicle clustering, which is particularly conspicuous for the EGFP-tagged variant, resulting in a massive accumulation of synaptic vesicles in neuronal somata without altering the distribution of other organelles. Both endogenous and induced clusters co-localize with autophagy-related proteins such as Atg16L1, LC3B and Rab33B but not with other organelles. Furthermore, Atg16L1 appears to be a direct effector of Rab26 and binds Rab26 in its GTP-bound form, albeit only with low affinity. We propose that Rab26 selectively directs synaptic and secretory vesicles into preautophagosomal structures, suggesting the presence of a novel pathway for degradation of synaptic vesicles.DOI: http://dx.doi.org/10.7554/eLife.05597.001

Slit, the ligand for the Roundabout (Robo) receptors, is secreted from midline cells of the Drosophila central nervous system (CNS). It acts as a short-range repellent that controls midline crossing of axons and allows growth cones to select specific pathways along each side of the midline. In addition, Slit directs the migration of muscle precursors and ventral branches of the tracheal system, showing that it provides long-range activity beyond the limit of the developing CNS. Biochemical studies suggest that guidance activity requires cell-surface heparan sulfate to promote binding of mammalian Slit/Robo homologs. Here, we report that the Drosophila homolog of Syndecan (reviewed in ), a heparan sulfate proteoglycan (HSPG), is required for proper Slit signaling. We generated syndecan (sdc) mutations and show that they affect all aspects of Slit activity and cause robo-like phenotypes. sdc interacts genetically with robo and slit, and double mutations cause a synergistic strengthening of the single-mutant phenotypes. The results suggest that Syndecan is a necessary component of Slit/Robo signaling and is required in the Slit target cells.

We describe the molecular characterization and function of vielfä ltig (vfl ), a X-chromosomal gene that encodes a nuclear protein with six Krü ppel-like C2H2 zinc finger motifs. vfl transcripts are maternally contributed and ubiquitously distributed in eggs and preblastoderm embryos, excluding the germline precursor cells. Zygotically, vfl is expressed strongly in the developing nervous system, the brain, and in other mitotically active tissues. Vfl protein shows dynamic subcellular patterns during the cell cycle. In interphase nuclei, Vfl is associated with chromatin, whereas during mitosis, Vfl separates from chromatin and becomes distributed in a granular pattern in the nucleoplasm. Functional gain-offunction and lack-of-function studies show that vfl activity is necessary for normal mitotic cell divisions. Loss of vfl activity disrupts the pattern of mitotic waves in preblastoderm embryos, elicits asynchronous DNA replication, and causes improper chromosome segregation during mitosis. INTRODUCTIONZinc fingers constitute the most abundant structural motifs in the proteome predicted from the genome sequences of Saccharomyces cerevisiae, Drosophila melanogaster, and Caenorhabditis elegans (Rubin et al., 2000) as well as the draft human genomic sequences (Lander et al., 2001). Zinc finger proteins are best known as transcriptional regulators that participate in a variety of cellular activities such as development, differentiation, and tumor suppression. The most common form of zinc finger domain is the so called C2H2 domain, first identified in the basal transcription factor TFIIIA in Xenopus laevis (Miller et al., 1985) and subsequently found also in DNA-binding transcription factors regulating polymerase II-dependent gene expression (Rosenberg et al., 1985). The three-dimensional structure of the basic C2H2 zinc finger is a small domain composed of a ␤-hairpin followed by an ␣-helix, a structure that is held in place by a zinc ion. DNA-binding C2H2 zinc fingers generally occur as tandem arrays with a minimum of two fingers needed to specify the DNA-binding site (Choo and Klug, 1995). In addition to DNA-binding, zinc finger proteins have been implicated in RNA-binding, protein-protein interactions, and lipid binding (Lorick et al., 1999;Bach, 2000;Tucker et al., 2001).DNA-binding C2H2 zinc finger proteins contain proteinbinding domains that provide the basis for the assembly of regulatory complexes involved in chromatin remodeling and transcriptional regulation (Aasland et al., 1995;David et al., 1998). They are frequently expressed in distinct spatial and temporal patterns, and their subcellular localization was found to be regulated in a cell cycle-dependent manner. The entry of mitosis is characterized by the transcriptional shutdown (Prescott and Bender, 1962) that involves inactivation of the general transcription machinery (Segil et al., 1996;Bellier et al., 1997;Akoulitchev and Reinberg, 1998;Long et al., 1998) as well as gene-specific transcription factors during the G 2 /M transition during mitosis. F...