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Astroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation
How developing astroglia regulate postnatal axon growth is unknown. Here, the authors define an astroglial exosome surface HepaCAM contact mechanism in regulating axon growth and how its antagonization by ApoE coordinates early postnatal pyramidal neuronal development.
- Shijie Jin
- , Xuan Chen
- & Yongjie Yang
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Article
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Amphetamine disrupts dopamine axon growth in adolescence by a sex-specific mechanism in mice
Adolescent drug use augments psychiatric risk. Here the authors show that abused drugs dysregulate adolescent Netrin-1/DCC signaling, triggering ectopic long-distance dopamine axon growth in males while Netrin1 compensatory events protect females.
- Lauren M. Reynolds
- , Giovanni Hernandez
- & Cecilia Flores
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Subcellular second messenger networks drive distinct repellent-induced axon behaviors
Signals from extracellular cues orienting growing axons are thought to be integrated by second messenger molecules. Here, Baudet et al. instead demonstrate that distinct axon guidance cues induce cAMP, cGMP and Ca2+ signals restricted to separate cellular nanodomains.
- Sarah Baudet
- , Yvrick Zagar
- & Xavier Nicol
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Article
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Profilin and Mical combine to impair F-actin assembly and promote disassembly and remodeling
Actin-based structures in cells and tissues are built and maintained through a poorly understood balance between assembly and disassembly. Here, our findings provide insights into how factors known to promote these opposing effects dynamically integrate to shape cells and tissue systems.
- Elena E. Grintsevich
- , Giasuddin Ahmed
- & Jonathan R. Terman
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RHOA signaling defects result in impaired axon guidance in iPSC-derived neurons from patients with tuberous sclerosis complex
Patients with Tuberous Sclerosis Complex (TSC) show aberrant wiring of neuronal connections. Here, the authors generate iPSC-derived neurons from patients with TSC. TSC2 +/− neurons show impaired mTOR-independent RhoA signaling-mediated axon guidance.
- Timothy S. Catlett
- , Massimo M. Onesto
- & Timothy M. Gómez
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Neuronal processes and glial precursors form a scaffold for wiring the developing mouse cochlea
In developing embryos, axons grow through complex and dynamic terrains. Here, the authors show that spiral ganglion neurons in the developing mouse cochlea extend leading axons that interact with a scaffold of glial precursors, with follower axons fasciculating on top.
- N. R. Druckenbrod
- , E. B. Hale
- & L. V. Goodrich
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Dscam1 establishes the columnar units through lineage-dependent repulsion between sister neurons in the fly brain
Columns are the functional and morphological unit of the brain, but how neurons assemble into this structure was unclear. Here, the authors show that Dscam gene rewires neurons that derive from the same stem cell to establish columns through the process of lineage-dependent repulsion.
- Chuyan Liu
- , Olena Trush
- & Makoto Sato
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Nolz1 expression is required in dopaminergic axon guidance and striatal innervation
The mechanisms regulating midbrain dopaminergic innervation during development are unclear. Here, the authors showed that Nolz1 is required for axonal guidance of dopaminergic neurons during embryonic development of the mouse brain.
- Clement Soleilhavoup
- , Marco Travaglio
- & Lia Panman
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NELL2-Robo3 complex structure reveals mechanisms of receptor activation for axon guidance
Robo3 is a divergent, multifunctional member of the Robo receptor family that mediates axon guidance by its ligand NELL2 instead of the canonical Slit ligands. Here, the authors present the crystal structures of human Robo3 in complex with NELL1 and NELL2, and they show through biophysical and functional assays how NELL-Robo3 affinity and ligand-induced receptor multimerization control axon guidance activity.
- Joseph S. Pak
- , Zachary J. DeLoughery
- & Engin Özkan
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Transient callosal projections of L4 neurons are eliminated for the acquisition of local connectivity
It is traditionally believed that callosal and non-callosal fates are determined early after a neuron’s birth, and that cortical layer (L) 4 excitatory neurons of the primary somatosensory (S1) barrel cortex project only ipsilaterally. However, here authors demonstrate, using a novel axonal retrotracing strategy, that L4 neurons develop transient interhemispheric axons that are refined in an area- and layer-specific manner during postnatal development.
- N. S. De León Reyes
- , S. Mederos
- & M. Nieto
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Sphingolipid-dependent Dscam sorting regulates axon segregation
Little is known about the initial segregation of axonal and dendritic proteins during the differentiation of newly generated neurons. Here authors use a forward genetic screen to identify the role of sphingolipids in regulating the sub-cellular distribution of Dscam for neuronal patterning in Drosophila Mushroom Bodies
- Gaurav Goyal
- , Junfeng Zheng
- & Thomas Hummel
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Sema7A/PlxnCl signaling triggers activity-dependent olfactory synapse formation
The molecular mechanisms underlying synapse formation in the olfactory bulb are not fully understood. Here the authors demonstrate that semaphorin 7A on olfactory sensory neurons, and its receptor plexin C1 expressed on mitral and tufted cells, is required for correct synapse formation.
- Nobuko Inoue
- , Hirofumi Nishizumi
- & Hitoshi Sakano
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Transcriptional repression of Plxnc1 by Lmx1a and Lmx1b directs topographic dopaminergic circuit formation
Midbrain dopaminergic neurons (mDAs) in the VTA and SNpc project to different regions and form distinct circuits. Here the authors show that transcription factors Lmx1a, Lmx1b, and Otx2 control the axon guidance of mDAs and the segregation of mesolimbic and nigrostriatal dopaminergic pathways.
- Audrey Chabrat
- , Guillaume Brisson
- & Martin Lévesque
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Extrinsic mechanical forces mediate retrograde axon extension in a developing neuronal circuit
How neuronal migration and axon growth coordinate during development is only partially understood. Here the authors use quantitative imaging to characterise the morphogenesis of the zebrafish olfactory placode and report an unexpected phenomenon, whereby axons extend through the passive movement of neuron cell bodies away from tethered axon tips.
- M. A. Breau
- , I. Bonnet
- & S. Schneider-Maunoury
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Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish
Following spinal injury in zebrafish, non-neural cells establish an extracellular matrix to promote axon re-growth but how this is regulated is unclear. Here, the authors show that Wnt/β-catenin signaling in fibroblast-like cells at a lesion activates axon re-growth via deposition of Collagen XII.
- Daniel Wehner
- , Themistoklis M. Tsarouchas
- & Catherina G. Becker
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Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits
Molecular mechanisms controlling axonal growth cone behaviour are only partially understood. Here the authors reveal a role of an adaptor protein GIPC1 in Plexin-D1 receptor recycling, and show that this process is required for axon track formation and vascular patterning in mice.
- Katja Burk
- , Erik Mire
- & Fanny Mann
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Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes
Netrins are secreted guidance factors that promote axon outgrowth and orientation during nervous system development. Here the authors present structural and biological evidence that netrin-4 is not a guidance cue per se, but rather functions to modulate laminin-laminin interactions.
- Raphael Reuten
- , Trushar R. Patel
- & Manuel Koch
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A plasma membrane microdomain compartmentalizes ephrin-generated cAMP signals to prune developing retinal axon arbors
It is unclear what role cholesterol-enriched domains of the plasma membrane play in mediating the development of neuronal circuits. Here, the authors show that such domains localize ephrin-A-induced cAMP signals, causing the pruning of retinal ganglion cell axons.
- Stefania Averaimo
- , Ahlem Assali
- & Xavier Nicol
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Optimal myelin elongation relies on YAP activation by axonal growth and inhibition by Crb3/Hippo pathway
Molecular mechanisms regulating optimal myelin geometry are only partially understood. Here authors show that peripheral myelin growth is orchestrated by the Crb3/Hippo/YAP pathway, and that defects in YAP activation may underlie peripheral neuropathies caused by shorter myelin.
- Ruani N. Fernando
- , Laurent Cotter
- & Nicolas Tricaud
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Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity
In mature neurons the centrosome no longer functions as the main microtubule organizer and it is unclear how ordered microtubule arrays are assembled. Here, the authors show that in post-mitotic neurons this process depends on non-centrosomal nucleation mediated by the protein complex augmin and the nucleator gamma-TuRC.
- Carlos Sánchez-Huertas
- , Francisco Freixo
- & Jens Lüders
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Super-complexes of adhesion GPCRs and neural guidance receptors
FLRT proteins are known to interact with Lphns and Unc5s, mediating cell adhesion and repulsion respectively. Here the authors use crystallography, native mass spectrometry, molecular dynamics simulations and cell-based assays to show that these three proteins form large super-complexes with functions distinct from their smaller subcomplexes.
- Verity A. Jackson
- , Shahid Mehmood
- & Elena Seiradake
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Reversal of axonal growth defects in an extraocular fibrosis model by engineering the kinesin–microtubule interface
How mutations in β3-tubulin cause axonal growth defects in congenital fibrosis of the extraocular muscles type 3 remains elusive. Minoura et al. develop a model system using recombinant human tubulin that demonstrates a link between tubulin mutation, impaired kinesin motility and axonal growth defects.
- Itsushi Minoura
- , Hiroko Takazaki
- & Etsuko Muto
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Draxin from neocortical neurons controls the guidance of thalamocortical projections into the neocortex
During neural development thalamocortical axons follow corticofugal projections into the neocortex. Here, using a combination of knock down and rescue experiments, the authors show that Draxin expression in neocortical cells promotes thalamic axon projections from the internal capsule.
- Yohei Shinmyo
- , M. Asrafuzzaman Riyadh
- & Hideaki Tanaka
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Restoration of skilled locomotion by sprouting corticospinal axons induced by co-deletion of PTEN and SOCS3
A key pathological alteration after brain and spinal cord injury is the disruption of the corticospinal tract (CST) axons that control the voluntary movements. Here the authors show that activating the intrinsic regenerative ability by inhibiting PTEN and SOCS3 expression promotes robust sprouting growth and recovery of skilled locomotion after injury.
- Duo Jin
- , Yuanyuan Liu
- & Zhigang He
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Tuning of Ranvier node and internode properties in myelinated axons to adjust action potential timing
Action potential timing is fundamental to information processing, but its determinants are not fully understood. Here the authors demonstrate unexpected structural specializations of myelinated axons in the auditory brainstem that help to adjust action potential arrival time for sound localization.
- Marc C. Ford
- , Olga Alexandrova
- & Benedikt Grothe
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Nonsynaptic junctions on myelinating glia promote preferential myelination of electrically active axons
The myelin sheath on vertebrate axons is critical for neural impulse transmission, but whether electrically active axons are preferentially myelinated by glial cells, is not clear. Here the authors show that cultured oligodendrocytes preferentially myelinate electrically active axons via a mechanism dependent on nonsynaptic vesicular release of glutamate.
- Hiroaki Wake
- , Fernando C. Ortiz
- & R. Douglas Fields
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Reading out a spatiotemporal population code by imaging neighbouring parallel fibre axons in vivo
The spatiotemporal pattern of synaptic inputs is critical for synaptic integration and plasticity in neurons but whether these inputs are structured or random is not clear. Here the authors use in vivocalcium imaging to monitor the presynaptic activity of cerebellar parallel fibre axons and find clustered patterns of axonal activity during sensory processing.
- Christian D. Wilms
- & Michael Häusser
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Remodelling of spared proprioceptive circuit involving a small number of neurons supports functional recovery
In response to spinal cord injuries, limited functional recovery can be achieved but the new circuits that arise have not been characterized in detail. Here the authors show that synaptic connections between the ascending proprioceptive neurons and a small number of spared dorsal column neurons, can be remodeled after a cervical lesion to support functional recovery.
- Edmund R. Hollis II
- , Nao Ishiko
- & Yimin Zou
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ADAM metalloproteases promote a developmental switch in responsiveness to the axonal repellant Sema3A
The basic axonal wiring of the vertebrate nervous system is set up during embryonic development, and during this process axons gain or lose sensitivity to guidance cues. Here the authors show that in proprioceptive axons, two members of the ADAM metalloproteinase family promote loss of responsiveness to Sema3A, via cleavage of its receptor Neuropilin-1.
- Erez Romi
- , Irena Gokhman
- & Avraham Yaron
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Venous endothelin guides sympathetic innervation of the developing mouse heart
The innervation of the mouse heart by synaptic nerve terminals during development is critical for proper heart function. Here, Manousiouthakis et al.show that sympathetic axons follow veins to reach and innervate specific areas of the ventricular myocardium and that vascular-derived endothelins have a role as axon guidance cues in this process.
- Eleana Manousiouthakis
- , Monica Mendez
- & Takako Makita
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Local translation of TC10 is required for membrane expansion during axon outgrowth
Axon growth requires exocyst-dependent membrane expansion, however it is unclear how this process is spatially regulated. Gracias et al.show that axonal translation of the exocyst regulator TC10 is necessary for stimulated membrane growth, and propose that local translation coordinates membrane and cytoskeletal enlargement.
- Neilia G. Gracias
- , Nicole J. Shirkey-Son
- & Ulrich Hengst
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Plexin-A4-dependent retrograde semaphorin 3A signalling regulates the dendritic localization of GluA2-containing AMPA receptors
Semaphorin 3A is a guidance factor that is implicated in axonal and dendritic development. Here, Yamashita et al. show that semaphorin 3A retrograde signalling via plexin A and dynein drives the localization of AMPA receptors to the dendrites where they are crucial for proper dendritic development.
- Naoya Yamashita
- , Hiroshi Usui
- & Yoshio Goshima
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LIS1-dependent retrograde translocation of excitatory synapses in developing interneuron dendrites
Maturation of synaptic junctions is important for proper neuronal connections. Using live cell imaging, Okabeet al. show that interneuron dendrites extend filopodia-like projections and use microtubule-dependent retrograde transport to guide proper synaptic distribution on dendrites.
- Izumi Kawabata
- , Yutaro Kashiwagi
- & Shigeo Okabe
Structure and function of Semaphorin-5A glycosaminoglycan interactions