Molecular insights into the axon guidance molecules Sidestep and Beaten path.

The transmembrane protein Sidestep (Side) functions as a substrate-bound attractant for motor axons in . Outgrowing motor axons recognize Side Beaten path Ia (Beat) and migrate along Side-expressing tissues. Here, we report a structure-function analysis of these guidance molecules using a variety of mutant lines and transgenic constructs.

Rearrangements in the musculature correlate with jumping behaviour in legless Mediterranean fruit fly larvae Ceratitis capitata (Tephritidae).

Larvae of holometabolic insects evolved different crawling strategies depending on the presence or absence of larval legs or life style. A rather unusual mode of locomotion has independently evolved in legless larvae of several dipteran species. Maggots of the Mediterranean fruit fly Ceratitis capitata developed an effective jumping mechanism to increase locomotion speed or to deter predators during the search for suitable pupation sites.

Dynamic monitoring of vital functions and tissue re-organization in Saturnia pavonia (Lepidoptera, Saturniidae) during final metamorphosis by non-invasive MRI.

Magnetic resonance imaging (MRI) is the key whole-body imaging technology for observing processes within a living object providing excellent resolution and contrast between soft tissues. In the present work, we exploited the non-destructive properties of MRI to track longitudinally the dynamic changes that take place in developing pupae of the Emperor Moth (Saturnia pavonia) during the last days before eclosion. While in diapause pupae, body fluid was almost homogeneously distributed over the internal compartments, as soon as wings, legs, flight muscles and the head region were fully developed, a significant redistribution of water levels occurred between thoracic and abdominal regions.

Misregulation of Sidestep Leads to Uncontrolled Wiring of the Adult Neuromuscular System and Severe Locomotion Defects.

Holometabolic organisms undergo extensive remodelling of their neuromuscular system during metamorphosis. Relatively, little is known whether or not the embryonic guidance of molecules and axonal growth mechanisms are re-activated for the innervation of a very different set of adult muscles. Here, we show that the axonal attractant Sidestep (Side) is re-expressed during metamorphosis and is indispensable for neuromuscular wiring.

Axon Guidance and Collective Cell Migration by Substrate-Derived Attractants.

Neurons have evolved specialized growth structures to reach and innervate their target cells. These growth cones express specific receptor molecules that sense environmental cues and transform them into steering decisions. Historically, various concepts of axon guidance have been developed to better understand how axons reach and identify their targets.

Sidestep-induced neuromuscular miswiring causes severe locomotion defects in larvae.

Mutations in motor axon guidance molecules cause aberrant projection patterns of motor nerves. As most studies in have analysed these molecules in fixed embryos, the consequences for larval locomotion are entirely unexplored Here, we took advantage of ()-mutant larvae that display severe locomotion defects because of irreparable innervation errors. Mutations in affected all motor nerve branches and all body wall regions.

Impaired protein translation in Drosophila models for Charcot-Marie-Tooth neuropathy caused by mutant tRNA synthetases.

Dominant mutations in five tRNA synthetases cause Charcot-Marie-Tooth (CMT) neuropathy, suggesting that altered aminoacylation function underlies the disease. However, previous studies showed that loss of aminoacylation activity is not required to cause CMT. Here we present a Drosophila model for CMT with mutations in glycyl-tRNA synthetase (GARS).

Hierarchical microtubule organization controls axon caliber and transport and determines synaptic structure and stability.

The dimensions of axons and synaptic terminals determine cell-intrinsic properties of neurons; however, the cellular mechanisms selectively controlling establishment and maintenance of neuronal compartments remain poorly understood. Here, we show that two giant Drosophila Ankyrin2 isoforms, Ank2-L and Ank2-XL, and the MAP1B homolog Futsch form a membrane-associated microtubule-organizing complex that determines axonal diameter, supports axonal transport, and provides independent control of synaptic dimensions and stability. Ank2-L controls microtubule and synaptic stability upstream of Ank2-XL that selectively controls microtubule organization.

The PIKE homolog Centaurin gamma regulates developmental timing in Drosophila.

Phosphoinositide-3-kinase enhancer (PIKE) proteins encoded by the PIKE/CENTG1 gene are members of the gamma subgroup of the Centaurin superfamily of small GTPases. They are characterized by their chimeric protein domain architecture consisting of a pleckstrin homology (PH) domain, a GTPase-activating (GAP) domain, Ankyrin repeats as well as an intrinsic GTPase domain. In mammals, three PIKE isoforms with variations in protein structure and subcellular localization are encoded by the PIKE locus.

Redox switch for actin.

Oxidation of actin methionine residues by the oxidation-reduction enzyme Mical is known to lead to actin filament depolymerization. SelR enzymes are now shown to reduce these oxidized actin methionines, revealing a regulated redox reaction mechanism through which cells control the assembly and disassembly of actin filaments.

Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly.

Synapse formation and maturation requires bidirectional communication across the synaptic cleft. The trans-synaptic Neurexin-Neuroligin complex can bridge this cleft, and severe synapse assembly deficits are found in Drosophila melanogaster neuroligin (Nlg1, dnlg1) and neurexin (Nrx-1, dnrx) mutants. We show that the presynaptic active zone protein Syd-1 interacts with Nrx-1 to control synapse formation at the Drosophila neuromuscular junction.

The synaptic cytoskeleton in development and disease.

The cytoskeleton forms the backbone of neuronal architecture, sustaining its form and size, subcellular compartments and cargo logistics. The synaptic cytoskeleton can be categorized in the microtubule-based core cytoskeleton and the cortical membrane skeleton. While central microtubules form the fundamental basis for the construction of elaborate neuronal processes, including axons and synapses, cortical actin filaments are generally considered to function as mediators of synapse dynamics and plasticity.

Drosophila neuroligin 1 promotes growth and postsynaptic differentiation at glutamatergic neuromuscular junctions.

Precise apposition of presynaptic and postsynaptic domains is a fundamental property of all neuronal circuits. Experiments in vitro suggest that Neuroligins and Neurexins function as key regulatory proteins in this process. In a genetic screen, we recovered several mutant alleles of Drosophila neuroligin 1 (dnlg1) that cause a severe reduction in bouton numbers at neuromuscular junctions (NMJs).

Searching for guidance cues: follow the Sidestep trail.

Neuronal growth cones migrate along stereotypic pathways to find and select their correct targets. Although it is widely believed that attractive and repulsive guidance molecules provide directional cues for migrating growth cones, it is still only poorly understood how these factors cooperate in a spatial and temporal manner. We have recently proposed that Drosophila motor axons recognize and follow a Sidestep-labeled substrate pathway from the ventral nerve cord to their peripheral target muscles.

No sidesteps on a beaten track: motor axons follow a labeled substrate pathway.

The establishment of synaptic connections between motor neurons and muscle fibers is essential for controlled body movements in any higher organism. The wiring of the neuromuscular system in Drosophila serves as a model system for the identification of key regulatory proteins that control axon guidance and target recognition. Sidestep (Side) is a transmembrane protein of the immunoglobulin superfamily and plays a pivotal role in the coordination of motor axonal guidance decisions, as it functions as a target-derived attractant.

Drosophila motor axons recognize and follow a Sidestep-labeled substrate pathway to reach their target fields.

During development of the Drosophila nervous system, migrating motor axons contact and interact with different cell types before reaching their peripheral muscle fields. The axonal attractant Sidestep (Side) is expressed in most of these intermediate targets. Here, we show that motor axons recognize and follow Side-expressing cell surfaces from the ventral nerve cord to their target region.

Drosophila ankyrin 2 is required for synaptic stability.

Synaptic connections are stabilized through transsynaptic adhesion complexes that are anchored in the underlying cytoskeleton. The Drosophila neuromuscular junction (NMJs) serves as a model system to unravel genes required for the structural remodeling of synapses. In a mutagenesis screen for regulators of synaptic stability, we recovered mutations in Drosophila ankyrin 2 (ank2) affecting two giant Ank2 isoforms that are specifically expressed in the nervous system and associate with the presynaptic membrane cytoskeleton.

Drosophila MICAL regulates myofilament organization and synaptic structure.

The overall size and structure of a synaptic terminal is an important determinant of its function. In a large-scale mutagenesis screen, designed to identify Drosophila mutants with abnormally structured neuromuscular junctions (NMJs), we discovered mutations in Drosophila mical, a conserved gene encoding a multi-domain protein with a N-terminal monooxygenase domain. In mical mutants, synaptic boutons do not sprout normally over the muscle surface and tend to form clusters along synaptic branches and at nerve entry sites.

At the next stop sign turn right: the metalloprotease Tolloid-related 1 controls defasciculation of motor axons in Drosophila.

Navigation of motoneuronal growth cones toward the somatic musculature in Drosophila serves as a model system to unravel the molecular mechanisms of axon guidance and target selection. In a large-scale mutagenesis screen, we identified piranha, a motor axon guidance mutant that shows strong defects in the neuromuscular connectivity pattern. In piranha mutant embryos, permanent defasciculation errors occur at specific choice points in all motor pathways.

The expression pattern of the Drosophila vesicular glutamate transporter: a marker protein for motoneurons and glutamatergic centers in the brain.

To determine the functions of genes in distinct tissues during the development of Drosophila, it is often desirable to have genetic tools for targeted gene expression in restricted subsets of cells. Here, we report the identification of the enhancer trap line OK371-Gal4, which is expressed in a defined subset of neurons from embryonic stage 15 to adulthood. In the ventral nerve chord, it is expressed almost exclusively in motoneurons and in the brain in a limited number of neuronal clusters.

Highwire regulates presynaptic BMP signaling essential for synaptic growth.

Highwire (Hiw), a putative RING finger E3 ubiquitin ligase, negatively regulates synaptic growth at the neuromuscular junction (NMJ) in Drosophila. hiw mutants have dramatically larger synaptic size and increased numbers of synaptic boutons. Here we show that Hiw binds to the Smad protein Medea (Med).

wishful thinking encodes a BMP type II receptor that regulates synaptic growth in Drosophila.

We conducted a large-scale screen for Drosophila mutants that have structural abnormalities of the larval neuromuscular junction (NMJ). We recovered mutations in wishful thinking (wit), a gene that positively regulates synaptic growth. wit encodes a BMP type II receptor.