88 research outputs found

    Src family kinases are required for limb trajectory selection by spinal motor axons

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    Signal relay by guidance receptors at the axonal growth cone is a process essential for the assembly of a functional nervous system. We investigated the in vivo function of Src family kinases (SFKs) as growth cone guidance signaling intermediates in the context of spinal lateral motor column (LMC) motor axon projection toward the ventral or dorsal limb mesenchyme. Using in situ mRNA detection we determined that Src and Fyn are expressed in LMC motor neurons of chick and mouse embryos at the time of limb trajectory selection. Inhibition of SFK activity by C-terminal Src kinase (Csk) overexpression in chickLMCaxons using in ovo electroporation resulted inLMC axons selecting the inappropriate dorsoventral trajectory within the limb mesenchyme, with medial LMC axon projecting into the dorsal and ventral limb nerve with apparently random incidence. We also detected LMC axon trajectory choice errors in Src mutant mice demonstrating a nonredundant role for Src in motor axon guidance in agreement with gain and loss of Src function in chickLMCneurons which led to the redirection ofLMCaxons. Finally, Csk-mediated SFK inhibition attenuated the retargeting ofLMCaxons caused by EphA or EphB over-expression, implying the participation of SFKs in Eph-mediated LMC motor axon guidance. In summary, our findings demonstrate that SFKs are essential for motor axon guidance and suggest that they play an important role in relaying ephrin:Eph signals that mediate the selection of motor axon trajectory in the limb.This work was supported by a grant from the Canadian Institutes of Health Research (Institute of Genetics and Institute of Neurosciences, Mental Health, and Addiction) to A.K. (MOP-77556 and IG-74068)

    Aberrant lysosomal carbohydrate storage accompanies endocytic defects and neurodegeneration in Drosophila benchwarmer

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    Lysosomal storage is the most common cause of neurodegenerative brain disease in preadulthood. However, the underlying cellular mechanisms that lead to neuronal dysfunction are unknown. Here, we report that loss of Drosophila benchwarmer (bnch), a predicted lysosomal sugar carrier, leads to carbohydrate storage in yolk spheres during oogenesis and results in widespread accumulation of enlarged lysosomal and late endosomal inclusions. At the bnch larval neuromuscular junction, we observe similar inclusions and find defects in synaptic vesicle recycling at the level of endocytosis. In addition, loss of bnch slows endosome-to-lysosome trafficking in larval garland cells. In adult bnch flies, we observe age-dependent synaptic dysfunction and neuronal degeneration. Finally, we find that loss of bnch strongly enhances tau neurotoxicity in a dose-dependent manner. We hypothesize that, in bnch, defective lysosomal carbohydrate efflux leads to endocytic defects with functional consequences in synaptic strength, neuronal viability, and tau neurotoxicity

    Foxp1 and lhx1 coordinate motor neuron migration with axon trajectory choice by gating Reelin signalling.

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    Topographic neuronal maps arise as a consequence of axon trajectory choice correlated with the localisation of neuronal soma, but the identity of the pathways coordinating these processes is unknown. We addressed this question in the context of the myotopic map formed by limb muscles innervated by spinal lateral motor column (LMC) motor axons where the Eph receptor signals specifying growth cone trajectory are restricted by Foxp1 and Lhx1 transcription factors. We show that the localisation of LMC neuron cell bodies can be dissociated from axon trajectory choice by either the loss or gain of function of the Reelin signalling pathway. The response of LMC motor neurons to Reelin is gated by Foxp1- and Lhx1-mediated regulation of expression of the critical Reelin signalling intermediate Dab1. Together, these observations point to identical transcription factors that control motor axon guidance and soma migration and reveal the molecular hierarchy of myotopic organisation

    MultiPlaneNeRF: Neural Radiance Field with Non-Trainable Representation

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    NeRF is a popular model that efficiently represents 3D objects from 2D images. However, vanilla NeRF has some important limitations. NeRF must be trained on each object separately. The training time is long since we encode the object's shape and color in neural network weights. Moreover, NeRF does not generalize well to unseen data. In this paper, we present MultiPlaneNeRF -- a model that simultaneously solves the above problems. Our model works directly on 2D images. We project 3D points on 2D images to produce non-trainable representations. The projection step is not parametrized and a very shallow decoder can efficiently process the representation. Furthermore, we can train MultiPlaneNeRF on a large data set and force our implicit decoder to generalize across many objects. Consequently, we can only replace the 2D images (without additional training) to produce a NeRF representation of the new object. In the experimental section, we demonstrate that MultiPlaneNeRF achieves results comparable to state-of-the-art models for synthesizing new views and has generalization properties. Additionally, MultiPlane decoder can be used as a component in large generative models like GANs

    Current advances in~information quantum technologies - critical issues

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    This article reviews chosen topics related to the development of Information Quantum Technologies in the major areas of measurements, communications, and computing. These fields start to build their ecosystems which in the future will probably coalesce into a homogeneous quantum information layer consisting of such interconnected components as quantum internet, full size quantum computers with efficient error corrections and ultrasensitive quantum metrology nodes stationary and mobile. Today, however, the skepticism expressing many doubts about the realizability of this optimistic view fights with a cheap optimism pouring out of some popular press releases. Where is the truth? Financing of the IQT by key players in research, development and markets substantially strengthens the optimistic side. Keeping the bright side with some reservations, we concentrate on showing the FAST pace of IQT developments in such areas as biological sciences, quantum evolutionary computations, quantum internet and some of its components

    Current advances in~information quantum technologies - critical issues

    Get PDF
    This article reviews chosen topics related to the development of Information Quantum Technologies in the major areas of measurements, communications, and computing. These fields start to build their ecosystems which in the future will probably coalesce into a homogeneous quantum information layer consisting of such interconnected components as quantum internet, full size quantum computers with efficient error corrections and ultrasensitive quantum metrology nodes stationary and mobile. Today, however, the skepticism expressing many doubts about the realizability of this optimistic view fights with a cheap optimism pouring out of some popular press releases. Where is the truth? Financing of the IQT by key players in research, development and markets substantially strengthens the optimistic side. Keeping the bright side with some reservations, we concentrate on showing the FAST pace of IQT developments in such areas as biological sciences, quantum evolutionary computations, quantum internet and some of its components

    A Retino-retinal Projection Guided by Unc5c Emerged in Species with Retinal Waves

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    We thank D Baeza and M Herrera for mouse breeding, genotyping and help in in utero electroporation experiments and E Llorens and J Mullet for technical help in experiments involving ferrets. We also thank A Barco for discussion and comments on the manuscript. The laboratory of EH is funded with the following grants: (BFU2016-77605 from the National Grant Research Program, PROMETEO Program (2016/026) from Generalitat Valenciana, (PCIN2015-192-C02-02 from ERA-Net Program) and (ERC282329 from the European Research Council). Work in the laboratory of LMM and SS was supported by the National Grant Research Program (Grant BFU2014-58776-r), cofinanced by the European Regional Development Fund (ERDF). VMB holds a postdoctoral contract from the Regional Government. AJV is the recipient of a FPI fellowship from the National Grant Research Program. We also acknowledge the financial support received from the “Severo Ochoa” Program for Centers of Excellence in R&D (SEV-2013-0317). AK was supported by the Canadian Institutes for Health Research Operating Grants MOP-77556 and MOP-97758, as well as Brain Canada, Canadian Foundation for Innovation, and the W. Garfield Weston Foundation.Peer reviewedPublisher PD

    Cell-Type Specific Roles for PTEN in Establishing a Functional Retinal Architecture

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    BACKGROUND: The retina has a unique three-dimensional architecture, the precise organization of which allows for complete sampling of the visual field. Along the radial or apicobasal axis, retinal neurons and their dendritic and axonal arbors are segregated into layers, while perpendicular to this axis, in the tangential plane, four of the six neuronal types form patterned cellular arrays, or mosaics. Currently, the molecular cues that control retinal cell positioning are not well-understood, especially those that operate in the tangential plane. Here we investigated the role of the PTEN phosphatase in establishing a functional retinal architecture. METHODOLOGY/PRINCIPAL FINDINGS: In the developing retina, PTEN was localized preferentially to ganglion, amacrine and horizontal cells, whose somata are distributed in mosaic patterns in the tangential plane. Generation of a retina-specific Pten knock-out resulted in retinal ganglion, amacrine and horizontal cell hypertrophy, and expansion of the inner plexiform layer. The spacing of Pten mutant mosaic populations was also aberrant, as were the arborization and fasciculation patterns of their processes, displaying cell type-specific defects in the radial and tangential dimensions. Irregular oscillatory potentials were also observed in Pten mutant electroretinograms, indicative of asynchronous amacrine cell firing. Furthermore, while Pten mutant RGC axons targeted appropriate brain regions, optokinetic spatial acuity was reduced in Pten mutant animals. Finally, while some features of the Pten mutant retina appeared similar to those reported in Dscam-mutant mice, PTEN expression and activity were normal in the absence of Dscam. CONCLUSIONS/SIGNIFICANCE: We conclude that Pten regulates somal positioning and neurite arborization patterns of a subset of retinal cells that form mosaics, likely functioning independently of Dscam, at least during the embryonic period. Our findings thus reveal an unexpected level of cellular specificity for the multi-purpose phosphatase, and identify Pten as an integral component of a novel cell positioning pathway in the retina

    Przyczynek do rozmieszczenia pluskwiaków różnoskrzydłych (Hemiptera: Heteroptera) w Polsce - III

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    [A contribution to the distribution of true bugs (Hemiptera: Heteroptera) in Poland – III]. This paper is a continuation of a series of publications on the distribution of true bugs in Poland and includes new faunistic data for 306 species of true bugs. In total, data on 62 species previously unreported in 21 zoogeographical regions of Poland is presented, including some rarely collected: Brachyarthrum limitatum, Eurydema fieberi, Peritrechus gracilicornis, Stephanitis pyri, Tingis crispata. It is also noteworthy that this paper was largely prepared using citizen science, where many people (non-specialists in Heteroptera) collected data constituting almost 25% of the presented records. Importantly, the true bugs recorded in this way include species very rarely collected in Poland, and species alien to Polish fauna (e.g. Oxycarenus lavaterae, Nezara viridula and Halyomorpha halys). Due to the lack of funding being a significant obstacle to biodiversity studies in Poland, citizen science seems to be the only way to effectively monitor all the dynamic changes taking place in national entomofauna

    Uncoupling of EphA/ephrinA signaling and spontaneous activity in neural circuit wiring

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    Classic studies have proposed that genetically encoded programs and spontaneous activity play complementary but independent roles in the development of neural circuits. Recent evidence, however, suggests that these two mechanisms could interact extensively, with spontaneous activity affecting the expression and function of guidance molecules at early developmental stages. Here, using the developing chick spinal cord and the mouse visual system to ectopically express the inwardly rectifying potassium channel Kir2.1 in individual embryonic neurons, we demonstrate that cell-intrinsic blockade of spontaneous activity in vivo does not affect neuronal identity specification, axon pathfinding, or EphA/ephrinA signaling during the development of topographic maps. However, intrinsic spontaneous activity is critical for axon branching and pruning once axonal growth cones reach their correct topographic position in the target tissues. Our experiments argue for the dissociation of spontaneous activity from hard-wired developmental programs in early phases of neural circuit formation.This work was supported by grants from the Regional Government (Prometeo 2012-005) and the Spanish Government (BFU2010-16563) to E.H. (BFU2007-67834 and BFU2010-22220) to L.M., and from the European Research Council (ERC-2011-StG_20101109) to E.H. and (ERC-2009-StG_20081210) G.L.-B., I.B. and G.C. are Consolider-Ingenio fellows (CDS2007-023). A.K. is supported by the Canadian Institutes of Health Research (Operating Grant MOP-77556) and the Natural Sciences and Engineering Research Council of Canada. D.M. holds a Mexican Council for Science and Technology (Conacyt) graduate scholarship.Peer reviewe
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