Differential Modulation of Retinal Degeneration by Ccl2 and Cx3cr1 Chemokine Signalling

Microglia and macrophages are recruited to sites of retinal degeneration where local cytokines and chemokines determine protective or neurotoxic microglia responses. Defining the role of Ccl2-Ccr2 and Cx3cl1-Cx3cr1 signalling for retinal pathology is of particular interest because of its potential role in age-related macular degeneration (AMD). Ccl2, Ccr2, and Cx3cr1 signalling defects impair macrophage trafficking, but have, in several conflicting studies, been reported to show different degrees of age-related retinal degeneration. Ccl2/Cx3cr1 double knockout (CCDKO) mice show an early onset retinal degeneration and have been suggested as a model for AMD. In order to understand phenotypic discrepancies in different chemokine knockout lines and to study how defects in Ccl2 and/or Cx3cr1 signalling contribute to the described early onset retinal degeneration, we defined primary and secondary pathological events in CCDKO mice. To control for genetic background variability, we compared the original phenotype with that of single Ccl2, Cx3cr1 and Ccl2/Cx3cr1 double knockout mice obtained from backcrosses of CCDKO with C57Bl/6 mice. We found that the primary pathological event in CCDKO mice develops in the inferior outer nuclear layer independently of light around postnatal day P14. RPE and vascular lesions develop secondarily with increasing penetrance with age and are clinically similar to retinal telangiectasia not to choroidal neovascularisation. Furthermore, we provide evidence that a third autosomal recessive gene causes the degeneration in CCDKO mice and in all affected re-derived lines and subsequently demonstrated co-segregation of the naturally occurring RD8 mutation in the Crb1 gene. By comparing CCDKO mice with re-derived CCl2−/−/Crb1Rd8/RD8, Cx3cr1−/−/Crb1Rd8/RD8 and CCl2−/−/Cx3cr1−/−/Crb1Rd8/RD8 mice, we observed a differential modulation of the retinal phenotype by genetic background and both chemokine signalling pathways. These findings indicate that CCDKO mice are not a model of AMD, but a model for an inherited retinal degeneration that is differentially modulated by Ccl2-Ccr2 and Cx3cl1-Cx3cr1 chemokine signalling

Honeybee linguistics—a comparative analysis of the waggle dance among species of Apis

All honeybees use the waggle dance to recruit nestmates. Studies on the dance precision of Apis mellifera have shown that the dance is often imprecise. Two hypotheses have been put forward aimed at explaining this imprecision. The first argues that imprecision in the context of foraging is adaptive as it ensures that the dance advertises the same patch size irrespective of distance. The second argues that the bees are constrained in their ability to be more precise, especially when the source is nearby. Recent studies have found support for the latter hypothesis but not for the “tuned-error” hypothesis, as the adaptive hypothesis became known. Here we investigate intra-dance variation among Apis species. We analyse the dance precision of A. florea, A. dorsata, and A. mellifera in the context of foraging and swarming. A. mellifera performs forage dances in the dark, using gravity as point of reference, and in the light when dancing for nest sites, using the sun as point of reference. Both A. dorsata and A. florea are open-nesting species; they do not use a different point of reference depending on context. A. florea differs from both A. mellifera and A. dorsata in that it dances on a horizontal surface and does not use gravity but instead “points” directly toward the goal when indicating direction. Previous work on A. mellifera has suggested that differences in dance orientation and point of reference can affect dance precision. We find that all three species improve dance precision with increasing waggle phase duration, irrespective of differences in dance orientation, and point of reference. When dancing for sources nearby, dances are highly variable. When the distance increases, dance precision converges. The exception is dances performed by A. mellifera on swarms. Here, dance precision decreases as the distance increases. We also show that the size of the patch advertised increases with increasing distance, contrary to what is predicted under the tuned-error hypothesis