MEGF10 and MEGF11 mediate homotypic interactions required for mosaic spacing of retinal neurons

In many parts of the nervous system, neuronal somata display orderly spatial arrangements. In the retina, neurons of numerous individual subtypes form regular arrays called mosaics: they are less likely to be near neighbours of the same subtype than would occur by chance, resulting in 'exclusion zones' that separate them. Mosaic arrangements provide a mechanism to distribute each cell type evenly across the retina, ensuring that all parts of the visual field have access to a full set of processing elements. Remarkably, mosaics are independent of each other: although a neuron of one subtype is unlikely to be adjacent to another of the same subtype, there is no restriction on its spatial relationship to neighbouring neurons of other subtypes. This independence has led to the hypothesis that molecular cues expressed by specific subtypes pattern mosaics by mediating homotypic (within-subtype) short-range repulsive interactions. So far, however, no molecules have been identified that show such activity, so this hypothesis remains untested. Here we demonstrate in mouse that two related transmembrane proteins, MEGF10 and MEGF11, have critical roles in the formation of mosaics by two retinal interneuron subtypes, starburst amacrine cells and horizontal cells. MEGF10 and 11 and their invertebrate relatives Caenorhabditis elegans CED-1 and Drosophila Draper have hitherto been studied primarily as receptors necessary for engulfment of debris following apoptosis or axonal injury. Our results demonstrate that members of this gene family can also serve as subtype-specific ligands that pattern neuronal arrays.     

Active terahertz metamaterial devices

The development of artificially structured electromagnetic materials, termed metamaterials, has led to the realization of phenomena that cannot be obtained with natural materials. This is especially important for the technologically relevant terahertz (1 THz = 10(12) Hz) frequency regime; many materials inherently do not respond to THz radiation, and the tools that are necessary to construct devices operating within this range-sources, lenses, switches, modulators and detectors-largely do not exist. Considerable efforts are underway to fill this 'THz gap' in view of the useful potential applications of THz radiation. Moderate progress has been made in THz generation and detection; THz quantum cascade lasers are a recent example. However, techniques to control and manipulate THz waves are lagging behind. Here we demonstrate an active metamaterial device capable of efficient real-time control and manipulation of THz radiation. The device consists of an array of gold electric resonator elements (the metamaterial) fabricated on a semiconductor substrate. The metamaterial array and substrate together effectively form a Schottky diode, which enables modulation of THz transmission by 50 per cent, an order of magnitude improvement over existing devices.     

SAR11 marine bacteria require exogenous reduced sulphur for growth

Sulphur is a universally required cell nutrient found in two amino acids and other small organic molecules. All aerobic marine bacteria are known to use assimilatory sulphate reduction to supply sulphur for biosynthesis, although many can assimilate sulphur from organic compounds that contain reduced sulphur atoms. An analysis of three complete 'Candidatus Pelagibacter ubique' genomes, and public ocean metagenomic data sets, suggested that members of the ubiquitous and abundant SAR11 alphaproteobacterial clade are deficient in assimilatory sulphate reduction genes. Here we show that SAR11 requires exogenous sources of reduced sulphur, such as methionine or 3-dimethylsulphoniopropionate (DMSP) for growth. Titrations of the algal osmolyte DMSP in seawater medium containing all other macronutrients in excess showed that 1.5 x 10(8) SAR11 cells are produced per nanomole of DMSP. Although it has been shown that other marine alphaproteobacteria use sulphur from DMSP in preference to sulphate, our results indicate that 'Cand. P. ubique' relies exclusively on reduced sulphur compounds that originate from other plankton.     

A role for VEGF as a negative regulator of pericyte function and vessel maturation

Angiogenesis does not only depend on endothelial cell invasion and proliferation: it also requires pericyte coverage of vascular sprouts for vessel stabilization. These processes are coordinated by vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) through their cognate receptors on endothelial cells and vascular smooth muscle cells (VSMCs), respectively. PDGF induces neovascularization by priming VSMCs/pericytes to release pro-angiogenic mediators. Although VEGF directly stimulates endothelial cell proliferation and migration, its role in pericyte biology is less clear. Here we define a role for VEGF as an inhibitor of neovascularization on the basis of its capacity to disrupt VSMC function. Specifically, under conditions of PDGF-mediated angiogenesis, VEGF ablates pericyte coverage of nascent vascular sprouts, leading to vessel destabilization. At the molecular level, VEGF-mediated activation of VEGF-R2 suppresses PDGF-Rbeta signalling in VSMCs through the assembly of a previously undescribed receptor complex consisting of PDGF-Rbeta and VEGF-R2. Inhibition of VEGF-R2 not only prevents assembly of this receptor complex but also restores angiogenesis in tissues exposed to both VEGF and PDGF. Finally, genetic deletion of tumour cell VEGF disrupts PDGF-Rbeta/VEGF-R2 complex formation and increases tumour vessel maturation. These findings underscore the importance of VSMCs/pericytes in neovascularization and reveal a dichotomous role for VEGF and VEGF-R2 signalling as both a promoter of endothelial cell function and a negative regulator of VSMCs and vessel maturation.     

Dscam and Sidekick proteins direct lamina-specific synaptic connections in vertebrate retina

Synaptic circuits in the retina transform visual input gathered by photoreceptors into messages that retinal ganglion cells (RGCs) send to the brain. Processes of retinal interneurons (amacrine and bipolar cells) form synapses on dendrites of RGCs in the inner plexiform layer (IPL). The IPL is divided into at least 10 parallel sublaminae; subsets of interneurons and RGCs arborize and form synapses in just one or a few of them. These lamina-specific circuits determine the visual features to which RGC subtypes respond. Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules--Dscam (Down's syndrome cell adhesion molecule), DscamL (refs 6-9), Sidekick-1 and Sidekick-2 (ref. 10)--are expressed in chick by non-overlapping subsets of interneurons and RGCs that form synapses in distinct IPL sublaminae. Moreover, each protein is concentrated within the appropriate sublaminae and each mediates homophilic adhesion. Loss- and gain-of-function studies in vivo indicate that these IgSF members participate in determining the IPL sublaminae in which synaptic partners arborize and connect. Thus, vertebrate Dscams, like Drosophila Dscams, play roles in neural connectivity. Together, our results on Dscams and Sidekicks suggest the existence of an IgSF code for laminar specificity in retina and, by implication, in other parts of the central nervous system.     

A common mass scale for satellite galaxies of the Milky Way

The Milky Way has at least twenty-three known satellite galaxies that shine with luminosities ranging from about a thousand to a billion times that of the Sun. Half of these galaxies were discovered in the past few years in the Sloan Digital Sky Survey, and they are among the least luminous galaxies in the known Universe. A determination of the mass of these galaxies provides a test of galaxy formation at the smallest scales and probes the nature of the dark matter that dominates the mass density of the Universe. Here we use new measurements of the velocities of the stars in these galaxies to show that they are consistent with them having a common mass of about 10(7) within their central 300 parsecs. This result demonstrates that the faintest of the Milky Way satellites are the most dark-matter-dominated galaxies known, and could be a hint of a new scale in galaxy formation or a characteristic scale for the clustering of dark matter.