While it is well established that Semaphorin family proteins function as axon guidance ligands in invertebrates and vertebrates, several recent studies indicate that the Drosophila Semaphorin-1a (Sema1a), a transmembrane Semaphorin, can also function as a receptor during neural development. The regulator of Sema1a reverse signaling, however, remains unknown. In this study, we show that like Sema1a, the well known Semaphorin receptor Plexin A (PlexA), is required for the proper guidance of photoreceptor (R cell) axons in the Drosophila visual system. Loss of PlexA, like loss of semala, disrupted the association of R-cell growth cones in the optic lobe. Conversely, overexpression of PlexA, like overexpression of sema1a, induced the hyperfasciculation of R-cell axons. Unlike Sema1a, however, the cytoplasmic domain of PlexA is dispensable. Epistasis analysis suggests that PlexA functions upstream of semala. And PlexA and sema1a interact genetically with Rho1. We propose that PlexA regulates Semala reverse signaling in the Drosophila visual system.

No abstract

bThe anillin-related protein Bud4 of Saccharomyces cerevisiae is required for axial bud site selection by linking the axial landmark to the septins, which localize at the mother bud neck. Recent studies indicate that Bud4 plays a role in septin organization during cytokinesis. Here we show that Bud4 is also involved in septin organization during bud growth prior to cytokinesis, as bud4⌬ shs1⌬ cells displayed an elongated bud morphology and defective septin organization at 18°C. Bud4 overexpression also affected septin organization during bud growth in shs1⌬ cells at 30°C. Bud4 was previously thought to associate with the septins via its central region, while the C-terminal anillin-related region was not involved in septin association. Surprisingly, we found that the central region of Bud4 alone targets to the bud neck throughout the cell cycle, unlike full-length Bud4, which localizes to the bud neck only during G 2 /M phase. We identified the anillin-related region to be a second targeting domain that cooperates with the central region for proper septin association. In addition, the anillin-related region could largely mediate Bud4's function in septin organization during bud growth and bud site selection. We show that this region interacts with the C terminus of Bud3 and the two segments depend on each other for association with the septins. Moreover, like the bud4⌬ mutant, the bud3⌬ mutant genetically interacts with shs1⌬ and cdc12-6 mutants in septin organization, suggesting that Bud4 and Bud3 may cooperate in septin organization during bud growth. These observations provide new insights into the interaction of Bud4 with the septins and Bud3.

Rubus chingii Hu ( R. chingii ), referred to as “Fu-Pen-Zi” in Chinese, has great medicinal and dietary values since ancient times. The dried fruits of R. chingii have been widely used in traditional Chinese medicine (TCM) for the treatment of kidney enuresis and urinary frequency for centuries. According to current findings, R. chingii has been reported to contain a variety of chemical constituents, mostly triterpenoids, diterpenoids, flavonoids, and organic acids. These compounds have been demonstrated to be the major bioactive components responsible for pharmacological effects such as anticomplementary, anticancer, antioxidant, antimicrobial, and anti-inflammatory functions. Therefore, this review focused on the up-to-date published data of the literature about R. chingii and comprehensively summarized its phytochemistry, pharmacology, quality control, and toxicity to provide a beneficial support to its further investigations and applications in medicines and foods.

There are intense interests in discovering proregenerative medicine leads that can promote cardiac differentiation and regeneration, as well as repair damaged heart tissues. We have combined zebrafish embryo-based screens with cardiomyogenesis assays to discover selective small molecules that modulate heart development and regeneration with minimal adverse effects. Two related compounds with novel structures, named as Cardiomogen 1 and 2 (CDMG1 and CDMG2), were identified for their capacity to promote myocardial hyperplasia through expansion of the cardiac progenitor cell population. We find that Cardiomogen acts as a Wnt inhibitor by targeting β-catenin and reducing Tcf/Lef-mediated transcription in cultured cells. CDMG treatment of amputated zebrafish hearts reduces nuclear β-catenin in injured heart tissue, increases cardiomyocyte (CM) proliferation, and expedites wound healing, thus accelerating cardiac muscle regeneration. Importantly, Cardiomogen can alleviate the functional deterioration of mammalian hearts after myocardial infarction. Injured hearts exposed to CDMG1 display increased newly formed CMs and reduced fibrotic scar tissue, which are in part attributable to the β-catenin reduction. Our findings indicate Cardiomogen as a Wnt inhibitor in enhancing injury-induced CM proliferation and heart regeneration, highlighting the values of embryo-based small molecule screens in discovery of effective and safe medicine leads.

Establishment of synaptic connections in the neuropils of the developing nervous system requires the coordination of specific neuriteneurite interactions (i.e., axon-axon, dendrite-dendrite and axon-dendrite interactions). The molecular mechanisms underlying coordination of neurite-neurite interactions for circuit assembly are incompletely understood. In this report, we identify a novel Ig superfamily transmembrane protein that we named Borderless (Bdl), as a novel regulator of neurite-neurite interactions in Drosophila. Bdl induces homotypic cell-cell adhesion in vitro and mediates neurite-neurite interactions in the developing visual system. Bdl interacts physically and genetically with the Ig transmembrane protein Turtle, a key regulator of axonal tiling. Our results also show that the receptor tyrosine phosphatase leukocyte common antigen-related protein (LAR) negatively regulates Bdl to control synaptic-layer selection. We propose that precise regulation of Bdl action coordinates neurite-neurite interactions for circuit formation in Drosophila.

No abstract

BackgroundProper adjustment of moving direction after external mechanical stimulation is essential for animals to avoid danger (e.g. predators), and thus is vital for survival. This process involves sensory inputs, central processing and motor outputs. Recent studies have made considerable progress in identifying mechanosensitive neurons and mechanosensation receptor proteins. Our understandings of molecular and cellular mechanisms that link mechanosensation with the changes in moving direction, however, remain limited.ResultsIn this study, we investigate the control of movement adjustment in Drosophila. In response to gentle touch at the anterior segments, Drosophila larvae reorient and select a new direction for forward movement. The extent of change in moving direction is correlated with the intensity of tactile stimuli. Sensation of gentle touch requires chordotonal organs and class IV da neurons. Genetic analysis indicates an important role for the evolutionarily conserved immunoglobulin (Ig) superfamily protein Turtle (Tutl) to regulate touch-initiated directional change. Tutl is required specifically in post-mitotic neurons at larval stage after the completion of embryonic development. Circuit breaking analysis identified a small subset of Tutl-positive neurons that are involved in the adjustment of moving direction.ConclusionWe identify Tutl and a small subset of CNS neurons in modulating directional change in response to gentle touch. This study presents an excellent starting point for further dissection of molecular and cellular mechanisms controlling directional adjustment after mechanical stimulation.