The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform
Kang Shen - One of the best experts on this subject based on the ideXlab platform.
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Setting up presynaptic structures at specific positions.
Current opinion in neurobiology, 2010Co-Authors: Kang ShenAbstract:Precise formation of presynaptic structures at specific loci is critical for correctly wiring neuronal circuits. Recent findings have gradually revealed how essential cues from different sources inform the axon to define the presynaptic domain and to choose its postsynaptic target. Here, we review key molecular regulators which mediate instructive or repellent signals from multiple sources including the target Cells, local Guidepost Cells, and distal guiding tissues.
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Building a synapse: lessons on synaptic specificity and presynaptic assembly from the nematode C. elegans.
Current opinion in neurobiology, 2008Co-Authors: Milica A. Margeta, Kang Shen, Brock GrillAbstract:Synapses are specialized sites of cell contact that mediate information flow between neurons and their targets. Genetic screens in the nematode C. elegans have led to the discovery of a number of molecules required for synapse patterning and assembly. Recent studies have demonstrated the importance of Guidepost Cells in the positioning of presynaptic sites at specific locations along the axon. Interestingly, these Guideposts can promote or inhibit synapse formation, and do so by utilizing transmembrane adhesion molecules or secreted factors that act over relatively larger distances. Once the decision of where to build a presynaptic terminal has been made, key molecules are recruited to assemble synaptic vesicles and active zone proteins at that site. Multiple steps of this process are regulated by ubiquitin ligase complexes. Interestingly, some of the molecules involved in presynaptic assembly also play roles in regulating axon polarity and outgrowth, suggesting that different neurodevelopmental processes are molecularly integrated.
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Synaptic specificity is generated by the synaptic Guidepost protein SYG-2 and its receptor, SYG-1.
Cell, 2004Co-Authors: Kang Shen, Richard D. Fetter, Cornelia I BargmannAbstract:Synaptic connections in the nervous system are directed onto specific cellular and subcellular targets. Synaptic Guidepost Cells in the C. elegans vulval epithelium drive synapses from the HSNL motor neuron onto adjacent target neurons and muscles. Here, we show that the transmembrane immunoglobulin superfamily protein SYG-2 is a central component of the synaptic Guidepost signal. SYG-2 is expressed transiently by primary vulval epithelial Cells during synapse formation. SYG-2 binds SYG-1, the receptor on HSNL, and directs SYG-1 accumulation and synapse formation to adjacent regions of HSNL. syg-1 and syg-2 mutants have defects in synaptic specificity; the HSNL neuron forms fewer synapses onto its normal targets and forms ectopic synapses onto inappropriate targets. Misexpression of SYG-2 in secondary epithelial Cells causes aberrant accumulation of SYG-1 and synaptic markers in HSNL adjacent to the SYG-2-expressing Cells. Our results indicate that local interactions between immunoglobulin superfamily proteins can determine specificity during synapse formation.
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the immunoglobulin superfamily protein syg 1 determines the location of specific synapses in c elegans
Cell, 2003Co-Authors: Kang Shen, Cornelia I BargmannAbstract:During nervous system development, neurons form reproducible synapses onto specific targets. Here, we analyze the development of stereotyped synapses of the C. elegans HSNL neuron in vivo. Postsynaptic neurons and muscles were not required for accurate synaptic vesicle clustering in HSNL. Instead, vulval epithelial Cells that contact HSNL act as synaptic Guidepost Cells that direct HSNL presynaptic vesicles to adjacent regions. The mutant syg-1(ky652) has defects in synapse formation that resemble those in animals that lack vulval epithelial Cells: HSNL synaptic vesicles fail to accumulate at normal synaptic locations and form ectopic anterior clusters. syg-1 encodes an immunoglobulin superfamily protein that acts in the presynaptic HSNL axon. SYG-1 protein is localized to the site of future synapses, where it initiates synapse formation and localizes synaptic connections in response to the epithelial signal. SYG-1 is related to Drosophila IrreC and vertebrate NEPH1 proteins, which mediate cell-cell recognition in diverse developmental contexts.
Cornelia I Bargmann - One of the best experts on this subject based on the ideXlab platform.
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Synaptic specificity is generated by the synaptic Guidepost protein SYG-2 and its receptor, SYG-1.
Cell, 2004Co-Authors: Kang Shen, Richard D. Fetter, Cornelia I BargmannAbstract:Synaptic connections in the nervous system are directed onto specific cellular and subcellular targets. Synaptic Guidepost Cells in the C. elegans vulval epithelium drive synapses from the HSNL motor neuron onto adjacent target neurons and muscles. Here, we show that the transmembrane immunoglobulin superfamily protein SYG-2 is a central component of the synaptic Guidepost signal. SYG-2 is expressed transiently by primary vulval epithelial Cells during synapse formation. SYG-2 binds SYG-1, the receptor on HSNL, and directs SYG-1 accumulation and synapse formation to adjacent regions of HSNL. syg-1 and syg-2 mutants have defects in synaptic specificity; the HSNL neuron forms fewer synapses onto its normal targets and forms ectopic synapses onto inappropriate targets. Misexpression of SYG-2 in secondary epithelial Cells causes aberrant accumulation of SYG-1 and synaptic markers in HSNL adjacent to the SYG-2-expressing Cells. Our results indicate that local interactions between immunoglobulin superfamily proteins can determine specificity during synapse formation.
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the immunoglobulin superfamily protein syg 1 determines the location of specific synapses in c elegans
Cell, 2003Co-Authors: Kang Shen, Cornelia I BargmannAbstract:During nervous system development, neurons form reproducible synapses onto specific targets. Here, we analyze the development of stereotyped synapses of the C. elegans HSNL neuron in vivo. Postsynaptic neurons and muscles were not required for accurate synaptic vesicle clustering in HSNL. Instead, vulval epithelial Cells that contact HSNL act as synaptic Guidepost Cells that direct HSNL presynaptic vesicles to adjacent regions. The mutant syg-1(ky652) has defects in synapse formation that resemble those in animals that lack vulval epithelial Cells: HSNL synaptic vesicles fail to accumulate at normal synaptic locations and form ectopic anterior clusters. syg-1 encodes an immunoglobulin superfamily protein that acts in the presynaptic HSNL axon. SYG-1 protein is localized to the site of future synapses, where it initiates synapse formation and localizes synaptic connections in response to the epithelial signal. SYG-1 is related to Drosophila IrreC and vertebrate NEPH1 proteins, which mediate cell-cell recognition in diverse developmental contexts.
Elke Neumann-haefelin - One of the best experts on this subject based on the ideXlab platform.
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Functional and Spatial Analysis of C. elegans SYG-1 and SYG-2, Orthologs of the Neph/Nephrin Cell Adhesion Module Directing Selective Synaptogenesis
PloS one, 2011Co-Authors: Nicola Wanner, Foteini Noutsou, Ralf Baumeister, Gerd Walz, Tobias B. Huber, Elke Neumann-haefelinAbstract:The assembly of specific synaptic connections represents a prime example of cellular recognition. Members of the Ig superfamily are among the most ancient proteins represented in the genomes of both mammalian and invertebrate organisms, where they constitute a trans-synaptic adhesion system. The correct connectivity patterns of the highly conserved immunoglobulin superfamily proteins nephrin and Neph1 are crucial for the assembly of functional neuronal circuits and the formation of the kidney slit diaphragm, a synapse-like structure forming the filtration barrier. Here, we utilize the nematode C. elegans model for studying the requirements of synaptic specificity mediated by nephrin-Neph proteins. In C. elegans, the nephrin/Neph1 orthologs SYG-2 and SYG-1 form intercellular contacts strictly in trans between epithelial Guidepost Cells and neurons specifying the localization of synapses. We demonstrate a functional conservation between mammalian nephrin and SYG-2. Expression of nephrin effectively compensated loss of syg-2 function in C. elegans and restored defective synaptic connectivity further establishing the C. elegans system as a valuable model for slit diaphragm proteins. Next, we investigated the effect of SYG-1 and SYG-2 trans homodimerization respectively. Strikingly, synapse assembly could be induced by homophilic SYG-1 but not SYG-2 binding indicating a critical role of SYG-1 intracellular signalling for morphogenetic events and pointing toward the dynamic and stochastic nature of extra- and intracellular nephrin-Neph interactions to generate reproducible patterns of synaptic connectivity.
Sonia Garel - One of the best experts on this subject based on the ideXlab platform.
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Trio GEF mediates RhoA activation downstream of Slit2 and coordinates telencephalic wiring
Development (Cambridge England), 2018Co-Authors: Stéphanie Backer, Sonia Garel, Ludmilla Lokmane, Camille Landragin, Marie Deck, Evelyne Bloch-gallegoAbstract:ABSTRACT Trio, a member of the Dbl family of guanine nucleotide exchange factors, activates Rac1 downstream of netrin 1/DCC signalling in axon outgrowth and guidance. Although it has been proposed that Trio also activates RhoA, the putative upstream factors remain unknown. Here, we show that Slit2 induces Trio-dependent RhoA activation, revealing a crosstalk between Slit and Trio/RhoA signalling. Consistently, we found that RhoA activity is hindered in vivo in Trio mutant mouse embryos. We next studied the development of the ventral telencephalon and thalamocortical axons, which have been previously shown to be controlled by Slit2. Remarkably, this analysis revealed that Trio knockout (KO) mice show phenotypes that bear strong similarities to the ones that have been reported in Slit2 KO mice in both Guidepost corridor Cells and thalamocortical axon pathfinding in the ventral telencephalon. Taken together, our results show that Trio induces RhoA activation downstream of Slit2, and support a functional role in ensuring the proper positioning of both Guidepost Cells and a major axonal tract. Our study indicates a novel role for Trio in Slit2 signalling and forebrain wiring, highlighting its role in multiple guidance pathways as well as in biological functions of importance for a factor involved in human brain disorders.
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Neuronal and microglial regulators of cortical wiring: usual and novel Guideposts
Frontiers in neuroscience, 2015Co-Authors: Paola Squarzoni, Morgane Sonia Thion, Sonia GarelAbstract:Neocortex functioning relies on the formation of complex networks that begins to be assembled during embryogenesis by highly stereotyped processes of cell migration and axonal navigation. The guidance of Cells and axons is driven by extracellular cues, released along by final targets or intermediate targets located along specific pathways. In particular, Guidepost Cells, originally described in the grasshopper, are considered discrete, specialized cell populations located at crucial decision points along axonal trajectories that regulate tract formation. These Cells are usually early-born, transient and act at short-range or via cell-cell contact. The vast majority of Guidepost Cells initially identified were glial Cells, which play a role in the formation of important axonal tracts in the forebrain, such as the corpus callosum, anterior and post-optic commissures as well as optic chiasm. In the last decades, tangential migrating neurons have also been found to participate in the guidance of principal axonal tracts in the forebrain. This is the case for several examples such as Guideposts for the lateral olfactory tract (LOT), corridor Cells, which open an internal path for thalamo-cortical axons and Cajal-Retzius Cells that have been involved in the formation of the entorhino-hippocampal connections. More recently, microglia, the resident macrophages of the brain, were specifically observed at the crossroads of important neuronal migratory routes and axonal tract pathways during forebrain development. We furthermore found that microglia participate to the shaping of prenatal forebrain circuits, thereby opening novel perspectives on forebrain development and wiring. Here we will review the last findings on already known Guidepost Cells populations and will discuss the role of microglia as a potentially new class of atypical Guidepost Cells.
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Inputs from the thalamocortical system on axon pathfinding mechanisms.
Current opinion in neurobiology, 2014Co-Authors: Sonia Garel, Guillermina López-benditoAbstract:Our understanding of axon pathfinding mechanisms has dramatically advanced thanks to the identification of guidance cues and receptors, and has been forged by the study of a limited number of model systems. Thalamocortical axons, which are essential for sensory processing and neocortical functioning, convey sensory information to the neocortex through a tightly controlled topographical interconnectivity between distinct thalamic neurons and cortical areas. Recent studies on this projection have provided mechanistic insights onto integrated processes controlling brain wiring: axons/Guidepost Cells interactions, building of reciprocal connections and the combinatorial activity of guidance cues. This review provides a selective overview of these novel features and stresses the interest of thalamocortical axons as an emerging model for studying axonal guidance and plasticity.
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Neuronal migration of Guidepost Cells
Cellular Migration and Formation of Neuronal Connections, 2013Co-Authors: Franck Bielle, Sonia GarelAbstract:Cell migration is a fundamental process in the emergence of brain architecture as it allows the distribution of all neurons of the central nervous system. In this chapter, we will review recent findings showing that neuronal migration is also a dynamic system for the display of axon guidance cues. We will show that migrating neuronal ‘Guidepost’ Cells are essential for the formation of major axonal tracts of the mouse telencephalon and discuss the implications of these findings with regard to brain morphogenesis, the evolution of axonal tracts, and pathological brain development.
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Mechanisms controlling the guidance of thalamocortical axons through the embryonic forebrain
The European journal of neuroscience, 2012Co-Authors: Zoltán Molnár, Sonia Garel, Guillermina López-bendito, Patricia F. Maness, David J PriceAbstract:Thalamocortical axons must cross a complex cellular terrain through the developing forebrain, and this terrain has to be understood for us to learn how thalamocortical axons reach their destinations. Selective fasciculation, Guidepost Cells and various diencephalic and telencephalic gradients have been implicated in thalamocortical guidance. As our understanding of the relevant forebrain patterns has increased, so has our knowledge of the guidance mechanisms. Our aim here is to review recent observations of cellular and molecular mechanisms related to: the growth of thalamofugal projections to the ventral telencephalon, thalamic axon avoidance of the hypothalamus and extension into the telencephalon to form the internal capsule, the crossing of the pallial-subpallial boundary, and the growth towards the cerebral cortex. We shall review current theories for the explanation of the maintenance and alteration of topographic order in the thalamocortical projections to the cortex. It is now increasingly clear that several mechanisms are involved at different stages of thalamocortical development, and each contributes substantially to the eventual outcome. Revealing the molecular and cellular mechanisms can help to link specific genes to details of actual developmental mechanisms.
Dieter Riethmacher - One of the best experts on this subject based on the ideXlab platform.
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Reallocation of Olfactory Cajal-Retzius Cells Shapes Neocortex Architecture
Neuron, 2016Co-Authors: Cristina A. De Frutos, Tatsumi Hirata, Morgane Sonia Thion, Guy Bouvier, Yoko Arai, Ludmilla Lokmane, Maryama Keita, Mario Garcia-dominguez, Patrick Charnay, Dieter RiethmacherAbstract:Summary The neocortex undergoes extensive developmental growth, but how its architecture adapts to expansion remains largely unknown. Here, we investigated how early born Cajal-Retzius (CR) neurons, which regulate the assembly of cortical circuits, maintain a dense superficial distribution in the growing neocortex. We found that CR cell density is sustained by an activity-dependent importation of olfactory CR Cells, which migrate into the neocortex after they have acted as axonal Guidepost Cells in the olfactory system. Furthermore, using mouse genetics, we showed that CR cell density severely affects the architecture of layer 1, a key site of input integration for neocortical networks, leading to an excitation/inhibition ratio imbalance. Our study reveals that neurons reenter migration several days after their initial positioning, thereby performing sequential developmental roles in olfactory cortex and neocortex. This atypical process is essential to regulate CR cell density during growth, which in turn ensures the correct wiring of neocortical circuitry. Video Abstract