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  1. Article ; Online: Synaptic promiscuity in brain development.

    Wolterhoff, Neele / Hiesinger, P Robin

    Current biology : CB

    2024  Volume 34, Issue 3, Page(s) R102–R116

    Abstract: Precise synaptic connectivity is a prerequisite for the function of neural circuits, yet individual neurons, taken out of their developmental context, readily form unspecific synapses. How does the genome encode brain wiring in light of this apparent ... ...

    Abstract Precise synaptic connectivity is a prerequisite for the function of neural circuits, yet individual neurons, taken out of their developmental context, readily form unspecific synapses. How does the genome encode brain wiring in light of this apparent contradiction? Synaptic specificity is the outcome of a long series of developmental processes and mechanisms before, during and after synapse formation. How much promiscuity is permissible or necessary at the moment of synaptic partner choice depends on the extent to which prior development restricts available partners or subsequent development corrects initially made synapses. Synaptic promiscuity at the moment of choice can thereby play important roles in the development of precise connectivity, but also facilitate developmental flexibility and robustness. In this review, we assess the experimental evidence for the prevalence and roles of promiscuous synapse formation during brain development. Many well-established experimental approaches are based on developmental genetic perturbation and an assessment of synaptic connectivity only in the adult; this can make it difficult to pinpoint when a given defect or mechanism occurred. In many cases, such studies reveal mechanisms that restrict partner availability already prior to synapse formation. Subsequently, at the moment of choice, factors including synaptic competency, interaction dynamics and molecular recognition further restrict synaptic partners. The discussion of the development of synaptic specificity through the lens of synaptic promiscuity suggests an algorithmic process based on neurons capable of promiscuous synapse formation that are continuously prevented from making the wrong choices, with no single mechanism or developmental time point sufficient to explain the outcome.
    MeSH term(s) Neurons/physiology ; Synapses/physiology ; Brain/physiology ; Neurogenesis
    Language English
    Publishing date 2024-02-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2023.12.037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Turnover of synaptic adhesion molecules.

    Nabavi, Melinda / Hiesinger, P Robin

    Molecular and cellular neurosciences

    2023  Volume 124, Page(s) 103816

    Abstract: Molecular interactions between pre- and postsynaptic membranes play critical roles during the development, function and maintenance of synapses. Synaptic interactions are mediated by cell surface receptors that may be held in place by trans-synaptic ... ...

    Abstract Molecular interactions between pre- and postsynaptic membranes play critical roles during the development, function and maintenance of synapses. Synaptic interactions are mediated by cell surface receptors that may be held in place by trans-synaptic adhesion or intracellular binding to membrane-associated scaffolding and signaling complexes. Despite their role in stabilizing synaptic contacts, synaptic adhesion molecules undergo turnover and degradation during all stages of a neuron's life. Here we review current knowledge about membrane trafficking mechanisms that regulate turnover of synaptic adhesion molecules and the functional significance of turnover for synapse development and function. Based on recent proteomics, genetics and imaging studies, synaptic adhesion molecules exhibit remarkably high turnover rates compared to other synaptic proteins. Degradation occurs predominantly via endolysosomal mechanisms, with little evidence for roles of proteasomal or autophagic degradation. Basal turnover occurs both during synaptic development and maintenance. Neuronal activity typically stabilizes synaptic adhesion molecules while downregulating neurotransmitter receptors based on turnover. In conclusion, constitutive turnover of synaptic adhesion molecules is not a necessarily destabilizing factor, but a basis for the dynamic regulation of trans-synaptic interactions during synapse formation and maintenance.
    MeSH term(s) Synapses/metabolism ; Synaptic Membranes ; Neurons/metabolism ; Cell Adhesion ; Signal Transduction ; Cell Adhesion Molecules, Neuronal/metabolism
    Chemical Substances Cell Adhesion Molecules, Neuronal
    Language English
    Publishing date 2023-01-14
    Publishing country United States
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1046640-x
    ISSN 1095-9327 ; 1044-7431
    ISSN (online) 1095-9327
    ISSN 1044-7431
    DOI 10.1016/j.mcn.2023.103816
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  3. Article ; Online: Lipid rafts, Rab GTPases, and a late endosomal checkpoint for plasma membrane recycling.

    Daumann, Ilsa-Maria / Hiesinger, P Robin

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 14, Page(s) e2302320120

    MeSH term(s) rab GTP-Binding Proteins/metabolism ; Endosomes/metabolism ; Cell Membrane/metabolism ; Membrane Microdomains/metabolism ; Protein Transport
    Chemical Substances rab GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2023-03-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2302320120
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  4. Article ; Online: Brain wiring: Love the one you're with.

    Fuchs, Joachim / Hiesinger, P Robin

    Current biology : CB

    2023  Volume 33, Issue 13, Page(s) R727–R729

    Abstract: Recent electron microscopy-based connectomes of the Caenorhabditis elegans nervous system provide a new opportunity to test classic models for the development of brain wiring. Statistical analyses now reveal that neuronal adjacencies (the contactome) can ...

    Abstract Recent electron microscopy-based connectomes of the Caenorhabditis elegans nervous system provide a new opportunity to test classic models for the development of brain wiring. Statistical analyses now reveal that neuronal adjacencies (the contactome) can partly predict synaptic connectivity (the connectome).
    MeSH term(s) Animals ; Love ; Brain ; Caenorhabditis elegans ; Connectome ; Research Design
    Language English
    Publishing date 2023-07-06
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2023.06.002
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  5. Article ; Online: Autophagy in synapse formation and brain wiring.

    Hassan, Bassem A / Hiesinger, P Robin

    Autophagy

    2023  Volume 19, Issue 10, Page(s) 2814–2816

    Abstract: A recent characterization of the role of autophagy in two different neuron types during brain development ... ...

    Abstract A recent characterization of the role of autophagy in two different neuron types during brain development in
    MeSH term(s) Animals ; Autophagy ; Neurons ; Synapses/physiology ; Neurogenesis ; Brain ; Drosophila
    Language English
    Publishing date 2023-03-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2023.2179778
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  6. Article ; Online: Brain wiring with composite instructions.

    Hiesinger, P Robin

    BioEssays : news and reviews in molecular, cellular and developmental biology

    2020  Volume 43, Issue 1, Page(s) e2000166

    Abstract: The quest for molecular mechanisms that guide axons or specify synaptic contacts has largely focused on molecules that intuitively relate to the idea of an "instruction." By contrast, "permissive" factors are traditionally considered background machinery ...

    Abstract The quest for molecular mechanisms that guide axons or specify synaptic contacts has largely focused on molecules that intuitively relate to the idea of an "instruction." By contrast, "permissive" factors are traditionally considered background machinery without contribution to the information content of a molecularly executed instruction. In this essay, I recast this dichotomy as a continuum from permissive to instructive actions of single factors that provide relative contributions to a necessarily collaborative effort. Individual molecules or other factors do not constitute absolute instructions by themselves; they provide necessary context for each other, thereby creating a composite that defines the overall instruction. The idea of composite instructions leads to two main conclusions: first, a composite of many seemingly permissive factors can define a specific instruction even in the absence of a single dominant contributor; second, individual factors are not necessarily related intuitively to the overall instruction or phenotypic outcome.
    MeSH term(s) Axons ; Brain ; Humans
    Language English
    Publishing date 2020-11-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.202000166
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    Zs.A 2024: Show issues Location:
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  7. Article ; Online: Neuronal filopodia: From stochastic dynamics to robustness of brain morphogenesis.

    Wit, Charlotte B / Hiesinger, P Robin

    Seminars in cell & developmental biology

    2022  Volume 133, Page(s) 10–19

    Abstract: Brain development relies on dynamic morphogenesis and interactions of neurons. Filopodia are thin and highly dynamic membrane protrusions that are critically required for neuronal development and neuronal interactions with the environment. Filopodial ... ...

    Abstract Brain development relies on dynamic morphogenesis and interactions of neurons. Filopodia are thin and highly dynamic membrane protrusions that are critically required for neuronal development and neuronal interactions with the environment. Filopodial interactions are typically characterized by non-deterministic dynamics, yet their involvement in developmental processes leads to stereotypic and robust outcomes. Here, we discuss recent advances in our understanding of how filopodial dynamics contribute to neuronal differentiation, migration, axonal and dendritic growth and synapse formation. Many of these advances are brought about by improved methods of live observation in intact developing brains. Recent findings integrate known and novel roles ranging from exploratory sensors and decision-making agents to pools for selection and mechanical functions. Different types of filopodial dynamics thereby reveal non-deterministic subcellular decision-making processes as part of genetically encoded brain development.
    MeSH term(s) Pseudopodia ; Neurogenesis/physiology ; Neurons ; Morphogenesis ; Brain
    Language English
    Publishing date 2022-04-06
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1312473-0
    ISSN 1096-3634 ; 1084-9521
    ISSN (online) 1096-3634
    ISSN 1084-9521
    DOI 10.1016/j.semcdb.2022.03.038
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  8. Article ; Online: Axonal self-sorting without target guidance in

    Agi, Egemen / Reifenstein, Eric T / Wit, Charlotte / Schneider, Teresa / Kauer, Monika / Kehribar, Melinda / Kulkarni, Abhishek / von Kleist, Max / Hiesinger, P Robin

    Science (New York, N.Y.)

    2024  Volume 383, Issue 6687, Page(s) 1084–1092

    Abstract: The idea of guidance toward a target is central to axon pathfinding and brain wiring in general. In this work, we show how several thousand axonal growth cones self-pattern without target-dependent guidance during neural superposition wiring ... ...

    Abstract The idea of guidance toward a target is central to axon pathfinding and brain wiring in general. In this work, we show how several thousand axonal growth cones self-pattern without target-dependent guidance during neural superposition wiring in
    MeSH term(s) Animals ; Axon Guidance ; Drosophila melanogaster/growth & development ; Growth Cones/physiology ; Neurons/physiology ; Pseudopodia/physiology
    Language English
    Publishing date 2024-03-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.adk3043
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  9. Article ; Online: The Evolution of Variability and Robustness in Neural Development.

    Hiesinger, P Robin / Hassan, Bassem A

    Trends in neurosciences

    2018  Volume 41, Issue 9, Page(s) 577–586

    Abstract: As in all biological systems, neurons and their networks must balance precision with variability. Phenotypic precision and phenotypic variability can both occur with remarkable robustness, where robustness is defined as the ability to tolerate ... ...

    Abstract As in all biological systems, neurons and their networks must balance precision with variability. Phenotypic precision and phenotypic variability can both occur with remarkable robustness, where robustness is defined as the ability to tolerate perturbation. Variability in genotype-phenotype mapping produces phenotypic variability despite identical genetic information. The resulting variability among genetically identical neurons can contribute to the robustness of brain development. Similarly, variability of genetically identical individuals can contribute to evolutionary robustness. We discuss here shared principles of developmental robustness and evolutionary robustness, and highlight scenarios where such principles result in neural networks that achieve robustness of precision or variability.
    MeSH term(s) Animals ; Biological Evolution ; Biological Variation, Population ; Brain/growth & development ; Genotype ; Humans ; Neural Pathways/growth & development
    Language English
    Publishing date 2018-06-04
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 282488-7
    ISSN 1878-108X ; 0378-5912 ; 0166-2236
    ISSN (online) 1878-108X
    ISSN 0378-5912 ; 0166-2236
    DOI 10.1016/j.tins.2018.05.007
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  10. Article ; Online: Wiring visual systems: common and divergent mechanisms and principles.

    Kolodkin, Alex L / Hiesinger, P Robin

    Current opinion in neurobiology

    2017  Volume 42, Page(s) 128–135

    Abstract: The study of visual systems has a rich history, leading to the discovery and understanding of basic principles underlying the elaboration of neuronal connectivity. Recent work in model organisms such as fly, fish and mouse has yielded a wealth of new ... ...

    Abstract The study of visual systems has a rich history, leading to the discovery and understanding of basic principles underlying the elaboration of neuronal connectivity. Recent work in model organisms such as fly, fish and mouse has yielded a wealth of new insights into visual system wiring. Here, we consider how axonal and dendritic patterning in columns and laminae influence synaptic partner selection in these model organisms. We highlight similarities and differences among disparate visual systems with the goal of identifying common and divergent principles for visual system wiring.
    MeSH term(s) Animals ; Axons/physiology ; Body Patterning ; Dendrites/physiology ; Models, Animal ; Neurons/cytology ; Neurons/physiology ; Visual Pathways/physiology
    Language English
    Publishing date 2017-01-05
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1078046-4
    ISSN 1873-6882 ; 0959-4388
    ISSN (online) 1873-6882
    ISSN 0959-4388
    DOI 10.1016/j.conb.2016.12.006
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