• MeSH
• členovci MeSH
• elektrofyziologie MeSH
• elektrolyty MeSH
• experimenty na zvířatech MeSH
• membránové potenciály MeSH
• nervová vlákna MeSH
• neurony MeSH

• MeSH
• autonomní nervový systém ultrastruktura   MeSH
• elektronová mikroskopie MeSH
• endoplazmatické retikulum MeSH
• kočky MeSH
• nervová vlákna ultrastruktura   MeSH
• techniky in vitro MeSH
• Check Tag
• kočky MeSH

• MeSH
• axony cytologie   fyziologie   MeSH
• biologický transport MeSH
• dyneiny MeSH
• mikrotubuly cytologie   MeSH
• myelinová pochva fyziologie   MeSH
• Schwannovy buňky cytologie   fyziologie   MeSH

• MeSH
• mícha anatomie a histologie   růst a vývoj   MeSH
• nervová vlákna myelinizovaná MeSH
• neuroglie MeSH
• plod MeSH

• MeSH
• cholinesterasy MeSH
• experimenty na zvířatech MeSH
• krysa rodu rattus MeSH
• nervová vlákna enzymologie   MeSH
• neurony enzymologie   MeSH
• šlachy enzymologie   inervace   MeSH
• Check Tag
• krysa rodu rattus MeSH

While axon fasciculation plays a key role in the development of neural networks, very little is known about its dynamics and the underlying biophysical mechanisms. In a model system composed of neurons grown ex vivo from explants of embryonic mouse olfactory epithelia, we observed that axons dynamically interact with each other through their shafts, leading to zippering and unzippering behavior that regulates their fasciculation. Taking advantage of this new preparation suitable for studying such interactions, we carried out a detailed biophysical analysis of zippering, occurring either spontaneously or induced by micromanipulations and pharmacological treatments. We show that zippering arises from the competition of axon-axon adhesion and mechanical tension in the axons, and provide the first quantification of the force of axon-axon adhesion. Furthermore, we introduce a biophysical model of the zippering dynamics, and we quantitatively relate the individual zipper properties to global characteristics of the developing axon network. Our study uncovers a new role of mechanical tension in neural development: the regulation of axon fasciculation.

• MeSH
• axonální fascikulace * MeSH
• axony fyziologie   MeSH
• biofyzikální jevy * MeSH
• biologické modely MeSH
• buněčná adheze MeSH
• čichová sliznice embryologie   MeSH
• kultivované buňky MeSH
• mechanický stres MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Central nervous system (CNS) axons lose their intrinsic ability to regenerate upon maturity, whereas peripheral nervous system (PNS) axons do not. A key difference between these neuronal types is their ability to transport integrins into axons. Integrins can mediate PNS regeneration, but are excluded from adult CNS axons along with their Rab11 carriers. We reasoned that exclusion of the contents of Rab11 vesicles including integrins might contribute to the intrinsic inability of CNS neurons to regenerate, and investigated this by performing laser axotomy. We identify a novel regulator of selective axon transport and regeneration, the ARF6 guanine-nucleotide-exchange factor (GEF) EFA6 (also known as PSD). EFA6 exerts its effects from a location within the axon initial segment (AIS). EFA6 does not localise at the AIS in dorsal root ganglion (DRG) axons, and in these neurons, ARF6 activation is counteracted by an ARF GTPase-activating protein (GAP), which is absent from the CNS, ACAP1. Depleting EFA6 from cortical neurons permits endosomal integrin transport and enhances regeneration, whereas overexpressing EFA6 prevents DRG regeneration. Our results demonstrate that ARF6 is an intrinsic regulator of regenerative capacity, implicating EFA6 as a focal molecule linking the AIS, signalling and transport.This article has an associated First Person interview with the first author of the paper.

• MeSH
• alfa řetězce integrinu genetika   metabolismus   MeSH
• amyloidový prekurzorový protein beta genetika   metabolismus   MeSH
• axonální transport genetika   MeSH
• dendrity metabolismus   ultrastruktura   MeSH
• embryo savčí MeSH
• iniciální segment axonu metabolismus   ultrastruktura   MeSH
• krysa rodu rattus MeSH
• malá interferující RNA genetika   metabolismus   MeSH
• mikrotubuly MeSH
• mozková kůra metabolismus   ultrastruktura   MeSH
• neurony metabolismus   ultrastruktura   MeSH
• potkani Sprague-Dawley MeSH
• primární buněčná kultura MeSH
• proteiny aktivující GTPasu genetika   metabolismus   MeSH
• rab proteiny vázající GTP genetika   metabolismus   MeSH
• signální transdukce MeSH
• spinální ganglia metabolismus   ultrastruktura   MeSH
• výměnné faktory guaninnukleotidů antagonisté a inhibitory   genetika   metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• degenerace nervu patologie   ultrastruktura   MeSH
• experimenty na zvířatech MeSH
• medulla oblongata patologie   ultrastruktura   MeSH
• nervová vlákna patologie   ultrastruktura   MeSH
• nervová zakončení účinky záření   ultrastruktura   MeSH
• neurony patologie   ultrastruktura   MeSH
• psi MeSH
• pyramidové dráhy MeSH
• Check Tag
• psi MeSH

Regulation of axon guidance and pruning of inappropriate synapses by class 3 semaphorins are key to the development of neural circuits. Collapsin response mediator protein 2 (CRMP2) has been shown to regulate axon guidance by mediating semaphorin 3A (Sema3A) signaling; however, nothing is known about its role in synapse pruning. Here, using newly generated crmp2-/- mice we demonstrate that CRMP2 has a moderate effect on Sema3A-dependent axon guidance in vivo, and its deficiency leads to a mild defect in axon guidance in peripheral nerves and the corpus callosum. Surprisingly, crmp2-/- mice display prominent defects in stereotyped axon pruning in hippocampus and visual cortex and altered dendritic spine remodeling, which is consistent with impaired Sema3F signaling and with models of autism spectrum disorder (ASD). We demonstrate that CRMP2 mediates Sema3F signaling in primary neurons and that crmp2-/- mice display ASD-related social behavior changes in the early postnatal period as well as in adults. Together, we demonstrate that CRMP2 mediates Sema3F-dependent synapse pruning and its dysfunction shares histological and behavioral features of ASD.

• MeSH
• dendritické trny MeSH
• membránové proteiny fyziologie   MeSH
• mezibuněčné signální peptidy a proteiny genetika   MeSH
• myši knockoutované MeSH
• myši MeSH
• neurony MeSH
• neuroplasticita MeSH
• poruchy autistického spektra * MeSH
• proteiny nervové tkáně genetika   fyziologie   MeSH
• semaforiny * MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• atrofie MeSH
• axony účinky léků   MeSH
• bílá hmota patologie   účinky léků   MeSH
• cílená molekulární terapie MeSH
• kongresy jako téma MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• randomizované kontrolované studie jako téma MeSH
• roztroušená skleróza * farmakoterapie   patofyziologie   MeSH
• šedá hmota patologie   účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• Publikační typ
• novinové články MeSH