Proteoglycan-Mediated Axon Degeneration Corrects Pretarget Topographic Sorting Errors

SummaryProper arrangement of axonal projections into topographic maps is crucial for brain function, especially in sensory systems. An important mechanism for map formation is pretarget axon sorting, in which topographic ordering of axons appears in tracts before axons reach their target, but this process remains poorly understood. Here, we show that selective axon degeneration is used as a correction mechanism to eliminate missorted axons in the optic tract during retinotectal development in zebrafish. Retinal axons are not precisely ordered during initial pathfinding but become corrected later, with missorted axons selectively fragmenting and degenerating. We further show that heparan sulfate is required non-cell-autonomously to correct missorted axons and that restoring its synthesis at late stages in a deficient mutant is sufficient to restore topographic sorting. These findings uncover a function for developmental axon degeneration in ordering axonal projections and identify heparan sulfate as a key regulator of that process

Trans-Axonal Signaling in Neural Circuit Wiring

The development of neural circuits is a complex process that relies on the proper navigation of axons through their environment to their appropriate targets. While axon–environment and axon–target interactions have long been known as essential for circuit formation, communication between axons themselves has only more recently emerged as another crucial mechanism. Trans-axonal signaling governs many axonal behaviors, including fasciculation for proper guidance to targets, defasciculation for pathfinding at important choice points, repulsion along and within tracts for pre-target sorting and target selection, repulsion at the target for precise synaptic connectivity, and potentially selective degeneration for circuit refinement. This review outlines the recent advances in identifying the molecular mechanisms of trans-axonal signaling and discusses the role of axon–axon interactions during the different steps of neural circuit formation

Cryptomelane formation from nanocrystalline vernadite precursor: a high energy X-ray scattering and transmission electron microscopy perspective on reaction mechanisms

International audienceBackground:Vernadite is a nanocrystalline and turbostratic phyllomanganate which is ubiquitous in the environ‑ment. Its layers are built of (MnO6)8− octahedra connected through their edges and frequently contain vacancies and(or) isomorphic substitutions. Both create a layer charge deficit that can exceed 1 valence unit per layer octahedron and thus induces a strong chemical reactivity. In addition, vernadite has a high affinity for many trace elements (e.g., Co, Ni, and Zn) and possesses a redox potential that allows for the oxidation of redox sensitive elements (e.g., As, Cr, Tl). As a result, vernadite acts as a sink for many trace metal elements. In the environment, vernadite is often found associated with tectomanganates (e.g., todorokite and cryptomelane) of which it is thought to be the precursor. The transformation mechanism is not yet fully understood however and the fate of metals initially contained in vernadite structure during this transformation is still debated. In the present work, the transformation of synthetic vernadite (δ‑MnO2) to synthetic cryptomelane under conditions analogous to those prevailing in soils (dry state, room tempera‑ture and ambient pressure, in the dark) and over a time scale of ~10years was monitored using high‑energy X‑ray scattering (with both Bragg‑rod and pair distribution function formalisms) and transmission electron microscopy

Multilevel Analysis in Rural Cancer Control: A Conceptual Framework and Methodological Implications

Mitochondria are abundantly detected at the growth cone, the dynamic distal tip of developing axons that directs growth and guidance. It is, however, poorly understood how mitochondrial dynamics relate to growth cone behavior in vivo, and which mechanisms are responsible for anchoring mitochondria at the growth cone during axon pathfinding. Here, we show that in retinal axons elongating along the optic tract in zebrafish, mitochondria accumulate in the central area of the growth cone and are occasionally observed in filopodia extending from the growth cone periphery. Mitochondrial behavior at the growth cone in vivo is dynamic, with mitochondrial positioning and anterograde transport strongly correlating with growth cone behavior and axon outgrowth. Using novel zebrafish mutant lines that lack the mitochondrial anchoring proteins Syntaphilin a and b, we further show that Syntaphilins contribute to mitochondrial immobilization at the growth cone. Syntaphilins are, however, not required for proper growth cone morphology and axon growth in vivo, indicating that Syntaphilin-mediated anchoring of mitochondria at the growth cone plays only a minor role in elongating axons

Phosphoprotéines de la famille de la stathmine et morphogenèse neuronale

Le développement des prolongements neuronaux requiert une réorganisation dynamique des microtubules. Les protéines de la famille de la stathmine (dont SCG10, SCLIP et RB3) participent au contrôle de la dynamique des microtubules en séquestrant la tubuline. Leur profil d expression dans le système nerveux suggère qu elles jouent des rôles distincts et complémentaires lors de la morphogenèse neuronale. Cette étude visait à mieux comprendre leur diversité fonctionnelle et a permis de caractériser les fonctions spécifiques de SCLIP dans l axonogenèse et la dendritogenèse. Nous avons ainsi démontré que SCLIP régule la morphogenèse axonale des neurones d hippocampe différemment d SCG10, contrôlant le développement de nouvelles branches et non la surface du cône de croissance. Nous avons de plus révélé que SCLIP est fortement exprimée dans les cellules de Purkinje lors du développement du cervelet et joue un rôle primordial dans leur développement dendritique. Ces résultats ouvrent ainsi de nouvelles perspectives quant aux régulations fonctionnelles des protéines de la famille de la stathmine dans les neurones.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Apport de l'Odontologie Légale dans l'identification de masse. Rôle du Service des Armées

BORDEAUX2-BU Sci.Homme/Odontol. (330632102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Suivi des grossesses exposées au Centre Régional de Pharmacovigilance de Caen (étude rétrospective de 979 dossiers)

CAEN-BU Médecine pharmacie (141182102) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

LE CARCINOME NEUROENDOCRINE CUTANE PRIMITIF (A PROPOS DE SIX OBSERVATIONS)

AMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Monoclonal antibodies to rhamnogalacturonan I backbone

International audienceMonoclonal antibodies were raised against rhamnogalacturonan I backbone, a pectin domain, using Arabidopsis thaliana seed mucilage-derived rhamnogalacturonan I oligosaccharides-BSA conjugates. Two monoclonal antibodies, designated INRA-RU1 and INRA-RU2, selected for further characterization, were specific for the backbone of rhamnogalacturonan I, displaying no binding activity against the other pectin domains i.e. homogalacturonans, galactans or arabinans. A range of oligosaccharides was prepared by enzymatic digestion of rhamnogalacturonan I isolated from Arabidopsis thaliana seed mucilage and from sugar beet pectin, purified by low-pressure chromatography and characterized by high-performance anion-exchange chromatography and mass spectrometry. These rhamnogalacturonan I oligomers were used to characterize the binding site of the two monoclonal antibodies by competitive inhibition. Both INRA-RU1 and INRA-RU2 showed maximal binding to the [-> 2)-alpha-l-rhamnosep-(1 -> 4)-alpha-d-galacturonic acid p-(1 ->](7) structural motif but differed in their minimum binding requirement. INRA-RU2 required at least two disaccharide (rhamnose-galacturonic acid) repeats for the antibody to bind, while INRA-RU1 required a minimum of six disaccharide repeats. Furthermore, the binding capacity of INRA-RU1 decreased steeply as the number of disaccharide repeats go beyond seven. Each of these antibodies reacted with hairy regions isolated from sugar beet pectin. Immunofluorescence microscopy indicated that both antibodies can be readily used to detect rhamnogalacturonan I epitopes in various cell wall sample