visualizing-live-drosophila-glial-neuromuscular-junction-with

Visualizing the Live <em>Drosophila</em> Glial-neuromuscular Junction with Fluorescent Dyes

Our project identified GFP labeled glial structures at the developing larval fly neuromuscular synapse. To look at development of live glial-nerve-muscle ...

The basal lamina is composed of molecules which physically interact to form a network that serves as a migrational scaffold for many cell types. In the developing peripheral nervous system of the grasshopper, neuronal growth cones are intimately associated with the basal lamina as they migrate. Laminin is a major component of the basal lamina and is a potent promoter of neurite outgrowth in vitro. However, it is unclear what the source of laminin is or how the distribution of laminin within the basal lamina is established. To address this question, grasshopper laminin subunit genes were cloned. As expected, laminin was found within the basal lamina throughout the embryo, in particular in the limb bud, where its expression is coincident with the outgrowth and guidance of the Tibial (Til) pioneer neurons. Surprisingly, the synthesis of beta and gamma chains of laminin was restricted to migratory mesodermal cells, while in other nonmigratory tissues, such as epithelium and presumptive muscle, beta and gamma chains of laminin were not detected. In spite of this, laminin immunoreactivity in the basal lamina appears uniform and is available as a substrate for axonal outgrowth.

Migrating mesoderm establish a uniform distribution of laminin in the developing grasshopper embryo.

Migrieren von Mesoderm stellen eine gleichm&#xE4;&#xDF;ige Verteilung von Laminin in der sich entwickelnden Embryo Heuschrecke.

Glia from many diverse organisms play a number of important roles during the development of the nervous system. Therefore, knowing the molecules that control glial cell function will further our understanding of the mechanisms that control nervous system development. We have isolated a novel gene in Drosophila melanogaster that is expressed in a subset of the peripheral glia. We call this gene "Fire exit" (Fie), as the glia that express this gene do so during a time when they mark the entry and exit point of axons at the CNS/PNS boundary. This subset of peripheral glia act as intermediate targets during pathfinding and migration of the sensory axons in particular. Fire exit has been cloned and found to encode a novel transmembrane protein. Fire exit belongs to a group of proteins identified in the Drosophila melanogaster and Anopheles gambiae databases which contain four predicted transmembrane domains and a shared intracellular motif. Mutations that remove the fire exit protein have no obvious disruption to glial function. On the other hand, glia expressing the Fire exit gene bridge the transition zone between CNS and PNS and play a role in sensory axon guidance. Therefore, it appears that, while the glia that express this protein mediate axon guidance, Fire exit itself plays a nonessential part in this function. A role for Fire exit in glial development may be suggested by its evolutionary relationship to a family of lysosome-associated proteins called LAPTMs and suggests that Fire exit may function in intracellular transport during glial development.

Fire exit is a potential four transmembrane protein expressed in developing Drosophila glia.

Notausgang ist ein potentieller vier Transmembran-Protein bei der Entwicklung von Drosophila Gliazellen exprimiert.

Peripheral glial cells in both vertebrates and insects are born centrally and travel large distances to ensheathe axons in the periphery. There is very little known about how this migration is carried out. In other cells, it is known that rearrangement of the Actin cytoskeleton is an integral part of cell motility, yet the distribution of Actin in peripheral glial cell migration in vivo has not been previously characterized. To gain an understanding of how glia migrate, we specifically labeled the peripheral glia of Drosophila melanogaster using an Actin-GFP marker and analyzed their development in the embryonic PNS. It was found that Actin cytoskeleton is dynamically rearranged during glial cell migration. The peripheral glia were observed to migrate as a continuous chain of cells, with the leading glial cells appearing to participate to the greatest extent in exploring the extracellular surroundings with filopodia-like Actin containing projections. We hypothesized that the small GTPases Rho, Rac and Cdc42 are involved in Actin cytoskeletal rearrangements that underlie peripheral glial migration and nerve ensheathement. To test this, transgenic forms of the GTPases were ectopically expressed specifically in the peripheral glia during their migration and wrapping phases. The effects on glial Actin-GFP distribution and the overall effects on glial cell migration and morphological development were assessed. We found that RhoA and Rac1 have distinct roles in peripheral glial cell migration and nerve ensheathement; however, Cdc42 does not have a significant role in peripheral glial development. RhoA and Rac1 gain-of-function and loss-of-function mutants had both disruption of glial cell development and secondary effects on sensory axon fasciculation. Together, Actin cytoskeletal dynamics is an integral part of peripheral glial migration and nerve ensheathement, and is mediated by RhoA and Rac1.

RhoA and Rac1 GTPases mediate the dynamic rearrangement of actin in peripheral glia.

GTPasen RhoA und Rac1 vermitteln die dynamische Umlagerung von Aktin in peripheren Gliazellen.

Septate junctions (SJs), similar to tight junctions, function as transepithelial permeability barriers. Gliotactin (Gli) is a cholinesterase-like molecule that is necessary for blood-nerve barrier integrity, and may, therefore, contribute to SJ development or function. To address this hypothesis, we analyzed Gli expression and the Gli mutant phenotype in Drosophila epithelia. In Gli mutants, localization of SJ markers neurexin-IV, discs large, and coracle are disrupted. Furthermore, SJ barrier function is lost as determined by dye permeability assays. These data suggest that Gli is necessary for SJ formation. Surprisingly, Gli distribution only colocalizes with other SJ markers at tricellular junctions, suggesting that Gli has a unique function in SJ development. Ultrastructural analysis of Gli mutants supports this notion. In contrast to other SJ mutants in which septa are missing, septa are present in Gli mutants, but the junction has an immature morphology. We propose a model, whereby Gli acts at tricellular junctions to bind, anchor, or compact SJ strands apically during SJ development.

Gliotactin, a novel marker of tricellular junctions, is necessary for septate junction development in Drosophila.

Gliotactin, ein neuartiger Marker f&#xFC;r tricellular Kreuzungen, ist notwendig f&#xFC;r septiert Kreuzung Entwicklung in Drosophila.

A major developmental role of peripheral glia is to mediate sensory axon guidance; however, it is not known whether sensory neurons influence peripheral glial development. To determine whether glia and neurons reciprocally interact during embryonic development, we ablated each cell type by overexpressing the apoptosis gene, grim, and observed the effects on peripheral nervous system (PNS) development. When neurons are ablated, glial defects occur as a secondary effect, and vice versa. Therefore glia and neurons are codependent during embryogenesis. To further explore glial-neuronal interactions, we genetically disrupted glial migration or differentiation and observed the secondary effects on sensory neuron development. Glial migration and ensheathment of PNS axons was blocked by overexpression of activated Rho GTPase, a regulator of actin dynamics. Here, sensory axons extended to the CNS without exhibiting gross pathfinding errors. In contrast, disrupting differentiation by expression of dominant-negative Ras GTPase in glia resulted in major sensory axon pathfinding errors, similar to those seen in glial ablations. Glial overexpression of transgenic components of the epidermal growth factor receptor (EGFR) signaling pathway yielded similar sensory neuron defects and also downregulated the expression of the glial marker Neuroglian. Mutant analysis also suggested that the EGFR ligands Spitz and Vein play roles in peripheral glial development. The observations support a model in which glia express genes necessary for sensory neuron development, and these genes are potentially under the control of the EGFR/Ras signaling pathway.

Reciprocal interactions between neurons and glia are required for Drosophila peripheral nervous system development.

Wechselseitige Interaktionen zwischen Neuronen und Gliazellen sind f&#xFC;r Drosophila peripheren Nervensystems Entwicklung erforderlich.

Drosophila gliotactin (Gli) is a 109-kDa transmembrane, cholinesterase-like adhesion molecule (CLAM), expressed in peripheral glia, that is crucial for formation of the blood-nerve barrier. The intracellular portion (Gli-cyt) was cloned and expressed in the cytosolic fraction of Escherichia coli BLR(DE3) at 45 mg/L and purified by Ni-NTA (nitrilotriacetic acid) chromatography. Although migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), under denaturing conditions, was unusually slow, molecular weight determination by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) confirmed that the product was consistent with its theoretical size. Gel filtration chromatography yielded an anomalously large Stokes radius, suggesting a fully unfolded conformation. Circular dichroism (CD) spectroscopy demonstrated that Gli-cyt was >50% unfolded, further suggesting a nonglobular conformation. Finally, 1D-(1)H NMR conclusively demonstrated that Gli-cyt possesses an extended unfolded structure. In addition, Gli-cyt was shown to possess charge and hydrophobic properties characteristic of natively unfolded proteins (i.e., proteins that, when purified, are intrinsically disordered under physiologic conditions in vitro).

The intracellular domain of the Drosophila cholinesterase-like neural adhesion protein, gliotactin, is natively unfolded.

Die intrazellul&#xE4;re Dom&#xE4;ne des Drosophila-Cholinesterase wie neuronale Adh&#xE4;sionsproteins, gliotactin wird ungefaltete.

In Drosophila, wing hairs are aligned in a distally oriented, parallel array. The frizzled pathway determines proximal-distal cell polarity in the wing; however, in frizzled pathway mutants, wing hairs remain parallel. How wing hairs align has not been determined. We have demonstrated a novel role for the septate junction proteins Gliotactin (Gli) and Coracle (Cora) in this process. Prior to prehair extension, Gli and Cora were restricted to basolateral membranes. During pupal prehair development, Gli and Cora transiently formed apical ribbons oriented from the distal wing tip to the proximal hinge. These ribbons were aligned beneath prehair bases and persisted for several hours. During this time, Gli was lost entirely from the basolateral domain. A Gliotactin mutation altered the apical polarization Gli and Cora and induced defects in hair alignment in pupal and adult stages. Genetic and cell biological assays demonstrated that Gli and Cora function to align hairs independently of frizzled. Taken together, our results indicate that Gli and Cora function as the first-identified members of a long-predicted, frizzled-independent parallel alignment mechanism. We propose a model whereby the apical polarization of Gli and Cora functions to stabilize and align prehairs relative to anterior-posterior cell boundaries during pupal wing development.

Transient apical polarization of Gliotactin and Coracle is required for parallel alignment of wing hairs in Drosophila.

Transient apikale Polarisierung der Gliotactin und Coracle wird f&#xFC;r parallele Ausrichtung der Fl&#xFC;gel Haare in Drosophila ben&#xF6;tigt.

Glial cells have diverse functions that are necessary for the proper development and function of complex nervous systems. During development, a variety of reciprocal signaling interactions between glia and neurons dictate all parts of nervous system development. Glia may provide attractive, repulsive, or contact-mediated cues to steer neuronal growth cones and ensure that neurons find their appropriate synaptic targets. In fact, both neurons and glia may act as migrational substrates for one another at different times during development. Also, the exchange of trophic signals between glia and neurons is essential for the proper bundling, fasciculation, and ensheathement of axons as well as the differentiation and survival of both cell types. The growing number of links between glial malfunction and human disease has generated great interest in glial biology. Because of its relative simplicity and the many molecular genetic tools available, Drosophila is an excellent model organism for studying glial development. This review will outline the roles of glia and their interactions with neurons in the embryonic nervous system of the fly.

Signaling in glial development: differentiation migration and axon guidance.

Signaling in Gliazellen Entwicklung: Migration und Differenzierung Axonen.

The protein family known as CLAMS (cholinesterase-like adhesion molecules) forms a novel class of heterophilic cell adhesion proteins. Family members are found through a wide range of metazoans and play a role during the development of multiple tissues. The majority of members of this family are transmembrane proteins with an extracellular domain that is conserved with cholinesterases including acetylcholinesterase. Yet all family members lack one or more of the residues that make up the catalytic triad necessary for enzymatic function. Therefore the conserved cholinesterase-like domain is not necessary for enzymatic function but does appear to play a role in heterophilic binding. CLAMS are expressed in a wide array of tissues and most family members appear to play a role in cell adhesion and junction formation. The development of junctions including septate junctions and synaptic junctions require CLAM family members such as Gliotactin and Neuroligins respectively. Modeling of the cholinesterase-like domain reveals that evolutionary changes to the binding pocket of the cholinesterase domain may produce a range of different ligand binding partners for CLAM family members. In this vein, previous chimera experiments and recent work has identified mutations in CLAM family members that affect the structure of the cholinesterase-like domain. These mutant forms affect protein function during the development of specialized junctions and confirm the role of the cholinesterase domain in mediating heterophilic binding.

Evolution of clams (cholinesterase-like adhesion molecules): structure and function during development.

Evolution der Muscheln (Cholinesterase-&#xE4;hnlichen Adh&#xE4;sionsmolek&#xFC;le): Struktur und Funktion w&#xE4;hrend der Entwicklung.

Gliazellen haben vielf&auml;ltige Funktionen, die notwendig f&uuml;r die richtige Entwicklung und Funktion des komplexen Nervensystemen. Verschiedene Insekten, vor allem der Fruchtfliege Drosophila Melanogaster und der Nachtfalter Manduca Sexta, haben n&uuml;tzliche Modelle der Gliazellen Funktion w&auml;hrend der Entwicklung zur Verf&uuml;gung gestellt. Dieser &Uuml;berpr&uuml;fung wird Beweise von Gliazellen Beitr&auml;ge zu embryonalen, visuelle, olfaktorische und Fl&uuml;gel-Entwicklung darlegen. Wir werden auch Beweise f&uuml;r nicht-Entwicklungsbiologie Funktionen von Insekt Glia, einschlie&szlig;lich der Bildung von Blut-Hirn-Schranke, hom&ouml;ostatischen Funktionen und m&ouml;gliche Beitr&auml;ge an synaptischen Funktion skizzieren. Gegebenenfalls werden wir auch &Auml;hnlichkeiten zwischen den Funktionen von Insekt Glia und vertebrate Gegenst&uuml;cke hinweisen.

Rollen der Glia im Nervensystem Drosophila.

Glial cells have diverse functions that are necessary for the proper development and function of complex nervous systems. Various insects, primarily the fruit fly Drosophila melanogaster and the moth Manduca sexta, have provided useful models of glial function during development. The present review will outline evidence of glial contributions to embryonic, visual, olfactory and wing development. We will also outline evidence for non-developmental functions of insect glia including blood-brain-barrier formation, homeostatic functions and potential contributions to synaptic function. Where relevant, we will also point out similarities between the functions of insect glia and their vertebrate counterparts.

Roles of glia in the Drosophila nervous system.

The tricellular junction (TCJ) forms at the convergence of pleated septate junctions (SJs) from three adjacent cells in polarized epithelia and is necessary for maintaining the transepithelial barrier. In Drosophila, the transmembrane protein Gliotactin was the first identified marker of the TCJ, but little is known about other molecular constituents. We now show that Gliotactin associates with Discs large at the TCJ in a Ca(2+)-dependent manner. Discs large is essential for the formation of the TCJ and the localization of Gliotactin. Surprisingly, Gliotactin localization at the TCJ was independent of its PDZ-binding motif and Gliotactin did not bind directly to Discs large. Therefore Gliotactin and Discs large association is through intermediary proteins at the TCJ. Gliotactin can associate with other septate junction proteins but this was detected only when Gliotactin was overexpressed and spread throughout the septate junction domain. Gliotactin overexpression and spread also resulted in a reduction of Discs large staining but not vice versa. These results suggest that Discs large participates in different protein interactions in the SJ and the TCJ. Finally this work supports a model where Gliotactin and Dlg are components of a larger protein complex that links the converging SJs with the TCJ to create the transepithelial barrier.

Gliotactin and Discs large form a protein complex at the tricellular junction of polarized epithelial cells in Drosophila.

Die Tricellular-Kreuzung (TCJ) bildet bei der Konvergenz der gefaltete septiert Kreuzungen (SJs) aus drei angrenzenden Zellen im polarisierten Epithelien und ist notwendig f&uuml;r die Aufrechterhaltung der transepithelialen-Barriere. Drosophila die Transmembraneprotein Gliotactin war die erste identifizierte Markierung von der TCJ, aber wenig &uuml;ber andere Molekulare Bestandteile bekannt ist. Wir zeigen nun, dass die Scheiben bei der TCJ Ca(2+)-abh&auml;ngigen Weise Gliotactin zuordnet. Gro&szlig;e Scheiben ist essentiell f&uuml;r die Bildung der TCJ und die Lokalisierung von Gliotactin. &Uuml;berraschenderweise Gliotactin Lokalisierung auf der TCJ war unabh&auml;ngig von seiner PDZ-Bindung-Motiv und Gliotactin nicht direkt an den Scheiben gro&szlig;e binden. Daher ist Gliotactin und Scheiben gro&szlig;en Vereinigung durch vermittelnde Proteine an die TCJ. Gliotactin kann mit anderen Proteinen septiert Kreuzung zuordnen, aber dies war nur w&auml;hrend der Gliotactin war Pleuramesotheliom und verbreitete sich in der gesamten Dom&auml;ne septiert Kreuzung erkannt. Gliotactin-&Uuml;berexpression und Verbreitung f&uuml;hrte auch zu einer Reduktion der Discs gro&szlig;e beflecken, aber nicht umgekehrt. Diese Ergebnisse legen nahe, dass gro&szlig;e Scheiben beteiligt sich an verschiedenen Protein-Interaktionen in der SJ und die TCJ. Schlie&szlig;lich unterst&uuml;tzt diese Arbeit ein wo Gliotactin und Dlg Bestandteil einer gr&ouml;&szlig;eren Proteinkomplex sind, verbindet die konvergierenden SJs mit der TCJ transepithelialen-Barriere zu erstellen.

Gliotactin und gro&szlig;e Scheiben bilden ein Proteinkomplex an der Tricellular Kreuzung der polarisierten epithelialen Zellen in Drosophila.

Glial cells play a wide range of essential roles in both nervous system development and function and has been reviewed recently (Parker and Auld, 2006). Glia provide an insulating sheath, either form or direct the formation of the blood-brain barrier, contribute to ion and metabolite homeostasis and provide guidance cues. Glial function often depends on the ability of glial cells to migrate toward specific locations during nervous system development. Work in nervous system development in insects, in particular in the fruit fly Drosophila melanogaster and the tobacco hornworm Manduca sexta, has provided significant insight into the roles of glia, although the molecular mechanisms underlying glial cell migration are being determined only now. Indeed, many of the processes and mechanisms discovered in these simpler systems have direct parallels in the development of vertebrate nervous systems. In this review, we first examine the developmental contexts in which invertebrate glial cell migration has been observed, we next discuss the characterized molecules required for proper glial cell migration, and we finally discuss future goals to be addressed in the study of glial cell development.

No pun intended: future directions in invertebrate glial cell migration studies.

Gliazellen spielen zahlreiche wesentliche Rollen in Nervensystem Entwicklung und Funktion und wurde vor kurzem &uuml;berarbeitet (Parker und Auld, 2006). Glia bieten eine isolierende H&uuml;lle, entweder Formular oder direkt die Bildung der Blut - Hirn-Schranke, Ionen und Metabolit Hom&ouml;ostase beitragen und Anleitung Hinweise geben. Gliazellen Funktion h&auml;ngt oft die F&auml;higkeit von Gliazellen gegen&uuml;ber bestimmten Orten w&auml;hrend der Entwicklung des Nervensystems zu migrieren. Arbeit im Nervensystem Entwicklung bei Insekten, leistete insbesondere in der Fruchtfliege Drosophila Melanogaster und der Tabak Hornworm Manduca Sexta, bedeutende Einblicke in die Rollen der Glia, obwohl die molekularen Mechanismen Gliazelle Migration erst jetzt ermittelt werden. Tats&auml;chlich haben viele Prozesse und Mechanismen, die in diese einfachere Systeme entdeckt direkte parallelen in der Entwicklung der Wirbeltiere Nervensystem. In diesem Bericht untersuchen wir zuerst die Entwicklungsst&ouml;rungen Kontexte, in denen Wirbellosen Gliazelle Migration festgestellt, wir diskutieren weiter erforderlich f&uuml;r die ordnungsgem&auml;&szlig;e Gliazelle Migration gekennzeichneten Molek&uuml;le, und wir diskutieren schlie&szlig;lich Ziele f&uuml;r die Zukunft in der Studie der Gliazelle Entwicklung zu richten.

Kein Wortspiel beabsichtigt: zuk&uuml;nftige Richtungen in wirbellosen Gliazellen Zelle Migrationsforschung.

The tricellular junction (TCJ) forms at the convergence of bicellular junctions from three adjacent cells in polarized epithelia and is necessary for maintaining the transepithelial barrier. In the fruitfly Drosophila, the TCJ is generated at the meeting point of bicellular septate junctions. Gliotactin was the first identified component of the TCJ and is necessary for TCJ and septate junction development. Gliotactin is a member of the neuroligin family and associates with the PDZ protein discs large. Beyond this interaction, little is known about the mechanisms underlying Gliotactin localization and function at the TCJ. In this study, we show that Gliotactin is phosphorylated at conserved tyrosine residues, a process necessary for endocytosis and targeting to late endosomes and lysosomes for degradation. Regulation of Gliotactin levels through phosphorylation and endocytosis is necessary as overexpression results in displacement of Gliotactin away from the TCJ throughout the septate junction domain. Excessive Gliotactin in polarized epithelia leads to delamination, paired with subsequent migration, and apoptosis. The apoptosis and the resulting compensatory proliferation resulting from high levels of Gliotactin are mediated by the Drosophila JNK pathway. Therefore, Gliotactin levels within the cell membrane are regulated to ensure correct protein localization and cell survival.

Control of Gliotactin localization and levels by tyrosine phosphorylation and endocytosis is necessary for survival of polarized epithelia.

Die Tricellular-Kreuzung (TCJ) bildet bei der Konvergenz der bicellular Kreuzungen aus drei angrenzenden Zellen im polarisierten Epithelien und ist notwendig f&uuml;r die Aufrechterhaltung der transepithelialen-Barriere. In der Fruitfly Taufliege wird die TCJ am Treffpunkt bicellular septiert Kreuzungen generiert. Gliotactin war der erste identifizierte Bestandteil von der TCJ und zum TCJ und septiert Kreuzung Entwicklung erforderlich ist. Gliotactin ist Mitglied der Neuroligin Familie und Mitarbeiter mit den gro&szlig;en PDZ-Protein-CDs. Jenseits dieser Interaktion ist wenig bekannt &uuml;ber die Mechanismen Gliotactin Lokalisierung und Funktion bei der TCJ. In dieser Studie zeigen wir, dass Gliotactin ein Prozess notwendig f&uuml;r Endozytose und gezielt zu sp&auml;ten Endosomen und Lysosomen Leistungsabfall bei konservierten Tyrosin R&uuml;ckst&auml;nde, phosphoryliert ist. Verordnung der Gliotactin Ebenen durch Phosphorylierung und Endozytose ist als eine &Uuml;berexpression f&uuml;hrt zu Verschiebung der Gliotactin Weg von der TCJ in der gesamten Dom&auml;ne septiert Kreuzung notwendig. &Uuml;berm&auml;&szlig;ige Gliotactin im polarisierten Epithelien f&uuml;hrt zu Delamination, gepaart mit anschlie&szlig;ende Migration und Apoptose. Die Apoptose und die resultierende kompensatorischen Vermehrung, die infolge der hohen Gliotactin sind durch die Taufliege JNK Pathway vermittelt. Daher werden Gliotactin Ebenen innerhalb der Zellmembran reguliert, um korrekte Proteinlokalisation und Zelle &uuml;berleben zu gew&auml;hrleisten.

Kontrolle der Gliotactin-Lokalisierung und Ebenen von Tyrosin-Phosphorylierung und Endozytose ist notwendig f&uuml;r das &Uuml;berleben der polarisierten Epithelien.

Peripheral nerve development involves multiple classes of glia that cooperate to form overlapping glial layers paired with the deposition of a surrounding extracellular matrix (ECM). The formation of this tubular structure protects the ensheathed axons from physical and pathogenic damage and from changes in the ionic environment. Integrins, a major family of ECM receptors, play a number of roles in the development of myelinating Schwann cells, one class of glia ensheathing the peripheral nerves of vertebrates. However, the identity and the role of the integrin complexes utilized by the other classes of peripheral nerve glia have not been determined in any animal. Here, we show that, in the peripheral nerves of Drosophila melanogaster, two integrin complexes (Î±PS2Î²PS and Î±PS3Î²PS) are expressed in the different glial layers and form adhesion complexes with integrin-linked kinase and Talin. Knockdown of the common beta subunit (Î²PS) using inducible RNAi in all glial cells results in lethality and glial defects. Analysis of integrin complex function in specific glial layers showed that loss of Î²PS in the outermost layer (the perineurial glia) results in a failure to wrap the nerve, a phenotype similar to that of Matrix metalloproteinase 2-mediated degradation of the ECM. Knockdown of Î²PS integrin in the innermost wrapping glia causes a loss of glial processes around axons. Together, our data suggest that integrins are employed in different glial layers to mediate the development and maintenance of the protective glial sheath in Drosophila peripheral nerves.

Integrins are necessary for the development and maintenance of the glial layers in the Drosophila peripheral nerve.

Peripherer Nerven Entwicklung betrifft mehrere Klassen von Glia, die Form, die &uuml;berlappende Gliazellen Ebenen gepaart mit der Absetzung eines umgebenden extrazellul&auml;ren Matrix (ECM) arbeiten zusammen. Die Bildung dieser r&ouml;hrenf&ouml;rmigen Struktur sch&uuml;tzt die Ensheathed Axone aus materiellen und pathogenen Sch&auml;den und Ver&auml;nderungen in der Ionischen Umgebung. Integrine, eine gro&szlig;e Familie von ECM-Rezeptoren, spielen einer Reihe von Rollen in der Entwicklung von Myelin, die Schwann-Zellen, einer Klasse von Glia-Ensheathing die peripheren Nerven der Wirbeltiere. Jedoch wurden die Identit&auml;t und die Rolle der Integrin-komplexe, indem Sie eine der anderen Klassen von peripheren Nerven Glia nicht in jedes Tier bestimmt. Hier zeigen wir, dass in den peripheren Nerven von Drosophila Melanogaster, zwei Integrin-komplexe (&alpha;PS2&beta;PS und &alpha;PS3&beta;PS) in den verschiedenen Gliazellen Schichten ausgedr&uuml;ckt werden und mit Integrin-linked Kinase und Talin Adh&auml;sion komplexe zu bilden. Niederschlag von der gemeinsamen Beta Untereinheit (&beta;PS) mit Induktion RNAi in alle Gliazellen f&uuml;hrt Letalit&auml;t und Gliazellen M&auml;ngel. Analyse der Integrin komplexe Funktion in bestimmten Gliazellen Schichten zeigte, Verlust des &beta;PS in die &auml;u&szlig;erste Schicht (die perineurial Glia) einen Fehler beim Wickeln Sie des Nervs, einem Ph&auml;notyp &auml;hnlich der Matrix Metalloprotease 2-vermittelten Degradation der ECM f&uuml;hrt. Niederschlag von &beta;PS Integrin im innersten Umh&uuml;llung Glia verursacht einen Verlust von Gliazellen Prozesse rund um Axone. Zusammen, zufolge unsere Daten Integrine in verschiedenen Gliazellen Schichten eingesetzt werden, um die Entwicklung und Wartung von den Gliazellen Schutzmantel in Drosophila peripheren Nerven zu vermitteln.

Article	Year
Migrating mesoderm establish a uniform distribution of laminin in the developing grasshopper embryo. Developmental biology\| PubMed ID: 12217318	2002
Fire exit is a potential four transmembrane protein expressed in developing Drosophila glia. Genesis (New York, N.Y. : 2000)\| PubMed ID: 12640618	2003
RhoA and Rac1 GTPases mediate the dynamic rearrangement of actin in peripheral glia. Development (Cambridge, England)\| PubMed ID: 12642488	2003
Gliotactin, a novel marker of tricellular junctions, is necessary for septate junction development in Drosophila. The Journal of cell biology\| PubMed ID: 12782681	2003
Reciprocal interactions between neurons and glia are required for Drosophila peripheral nervous system development. The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 12967983	2003
The intracellular domain of the Drosophila cholinesterase-like neural adhesion protein, gliotactin, is natively unfolded. Proteins\| PubMed ID: 14579366	2003
Transient apical polarization of Gliotactin and Coracle is required for parallel alignment of wing hairs in Drosophila. Developmental biology\| PubMed ID: 15501220	2004
Signaling in glial development: differentiation migration and axon guidance. Biochemistry and cell biology = Biochimie et biologie cellulaire\| PubMed ID: 15674437	2004
Evolution of clams (cholinesterase-like adhesion molecules): structure and function during development. Frontiers in bioscience : a journal and virtual library\| PubMed ID: 15970486	2005
Roles of glia in the Drosophila nervous system. Seminars in cell & developmental biology\| PubMed ID: 16420983	2006
Gliotactin and Discs large form a protein complex at the tricellular junction of polarized epithelial cells in Drosophila. Journal of cell science\| PubMed ID: 17032735	2006
No pun intended: future directions in invertebrate glial cell migration studies. Neuron glia biology\| PubMed ID: 18634577	2007
Control of Gliotactin localization and levels by tyrosine phosphorylation and endocytosis is necessary for survival of polarized epithelia. Journal of cell science\| PubMed ID: 21045109	2010
Integrins are necessary for the development and maintenance of the glial layers in the Drosophila peripheral nerve. Development (Cambridge, England)\| PubMed ID: 21828098	2011

Vanessa Auld

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