Brain development is orchestrated by both innate and experience-dependent mechanisms, but their relative contributions are difficult to disentangle. Here we asked if and how central visual areas are altered in a vertebrate brain depleted of any and all signals from retinal ganglion cells throughout development. We transcriptionally profiled neurons in pretectum, thalamus and other retinorecipient areas of larval zebrafish and searched for changes in lakritz mutants that lack all retinal connections.
View Article and Find Full Text PDFThe advent of multimodal brain atlases promises to accelerate progress in neuroscience by allowing in silico queries of neuron morphology, connectivity, and gene expression. We used multiplexed fluorescent in situ RNA hybridization chain reaction (HCR) technology to generate expression maps across the larval zebrafish brain for a growing set of marker genes. The data were registered to the Max Planck Zebrafish Brain (mapzebrain) atlas, thus allowing covisualization of gene expression, single-neuron tracings, and expertly curated anatomical segmentations.
View Article and Find Full Text PDFSocial affiliation emerges from individual-level behavioural rules that are driven by conspecific signals. Long-distance attraction and short-distance repulsion, for example, are rules that jointly set a preferred interanimal distance in swarms. However, little is known about their perceptual mechanisms and executive neural circuits.
View Article and Find Full Text PDFWe describe a simple and direct approach to measure the progression of single DNA replication forks in living cells by monitoring two fluorescently labeled loci downstream of an origin of replication. We employ this approach to investigate the roles of several leading and lagging strand factors in overall replisome function and show that fork progression is strongly dependent on proper maturation of Okazaki fragments. We also demonstrate how related cellular phenotypes, such as cell-cycle progression and the dynamics of sister chromatid cohesion, may be simultaneously monitored and correlated to DNA replication at the single-cell level.
View Article and Find Full Text PDFThe hexameric AAA ATPase VPS4 facilitates ESCRT III filament disassembly on diverse intracellular membranes. ESCRT III components and VPS4 have been localized to the ciliary transition zone and spindle poles and reported to affect centrosome duplication and spindle pole stability. How the canonical ESCRT pathway could mediate these events is unclear.
View Article and Find Full Text PDFTo enhance the antithrombotic properties of recombinant glycoprotein VI fragment crystallizable (GPVI-Fc), the authors incubated GPVI-Fc with anti-human Fc antibodies to cross-link the Fc tails of GPVI-Fc. Cross-linking potentiated the inhibition of human plaque- and collagen-induced platelet aggregation by GPVI-Fc under static and flow conditions without increasing bleeding time in vitro. Cross-linking with anti-human-Fc Fab2 was even superior to anti-human-Fc immunoglobulin G (IgG).
View Article and Find Full Text PDFMammalian cytokinetic abscission is mediated by the ESCRT membrane fission machinery. While much has been clarified on the topology and kinetics of abscission through high-resolution microscopy, key questions regarding the mechanism of abscission remain open. Here we apply cryogenic soft-X-ray tomography to elucidate new ultrastructural details in the intercellular membrane bridge connecting cells undergoing abscission.
View Article and Find Full Text PDFMost cellular organelles are highly dynamic and continuously undergo membrane fission and fusion to mediate their function. Documenting organelle dynamics under physiological conditions, therefore, requires high temporal resolution of the recording system. Concurrently, these structures are relatively small and determining their substructural organization is often impossible using conventional microscopy.
View Article and Find Full Text PDFBackground: Glycoprotein VI (GPVI) is the essential platelet collagen receptor in atherothrombosis, but its inhibition causes only a mild bleeding tendency. Thus, targeting this receptor has selective antithrombotic potential.
Objectives: This study sought to compare compounds interfering with platelet GPVI-atherosclerotic plaque interaction to improve current antiatherothrombotic therapy.