The Drosophila Wnt, Wingless, Provides an Essential Signal for Pre- and Postsynaptic Differentiation

Packard, Mary; Koo, Ellen Sumin; Gorczyca, Michael; Sharpe, Jade; Cumberledge, Susan; Budnik, Vivian

doi:10.1016/s0092-8674(02)01047-4

Cited by 386 publications

(467 citation statements)

References 62 publications

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“…It is curious that all of these distinct cell types express wingless. We have no evidence that axonally transported Wg functions in optic lobe development, as it does in the development of the neuromuscular junction (Packard et al, 2002). Partial elimination of wg + activity (by the use of a conditional wg ts allele) did not result in a specific defect in glial migration in the optic lobe (R.D.…”

Section: Discussionmentioning

confidence: 86%

An axon scaffold induced by retinal axons directs glia to destinations in theDrosophilaoptic lobe

Dearborn

Kunes

2004

Development

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In the developing Drosophila visual system, glia migrate into stereotyped positions within the photoreceptor axon target fields and provide positional information for photoreceptor axon guidance. Glial migration conversely depends on photoreceptor axons, as glia precursors stall in their progenitor zones when retinal innervation is eliminated. Our results support the view that this requirement for retinal innervation reflects a role of photoreceptor axons in the establishment of an axonal scaffold that guides glial cell migration. Optic lobe cortical axons extend from dorsal and ventral positions towards incoming photoreceptor axons and establish at least four separate pathways that direct glia to proper destinations in the optic lobe neuropiles. Photoreceptor axons induce the outgrowth of these scaffold axons. Most glia do not migrate when the scaffold axons are missing. Moreover, glia follow the aberrant pathways of scaffold axons that project aberrantly, as occurs in the mutant dachsous. The local absence of glia is accompanied by extensive apoptosis of optic lobe cortical neurons. These observations reveal a mechanism for coordinating photoreceptor axon arrival in the brain with the distribution of glia to multiple target destinations, where they are required for axon guidance and neuronal survival.

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Section: Discussionmentioning

confidence: 86%

An axon scaffold induced by retinal axons directs glia to destinations in theDrosophilaoptic lobe

Dearborn

Kunes

2004

Development

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“…Citron also interacts with SAP90/PSD-95 (43), and functions as Rho/Rac effector protein involved in the organization of the cytoskeleton (44). Wnt signaling pathway, which may be involved in the synaptic modeling and pre-and postsynaptic differentiation (45), possible exists in the PSD because we detect the Wnt inhibitor factor 1, which negatively regulates Wnt signaling (46). B-ras 1 is known to interact with NFand I -B and regulates their activity.…”

Section: Discussionmentioning

confidence: 92%

Proteomics Analysis of Rat Brain Postsynaptic Density

Hornshaw

Schors

et al. 2004

Journal of Biological Chemistry

235

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The postsynaptic density contains multiple protein complexes that together relay the presynaptic neurotransmitter input to the activation of the postsynaptic neuron. In the present study we took two independent proteome approaches for the characterization of the protein complement of the postsynaptic density, namely 1) two-dimensional gel electrophoresis separation of proteins in conjunction with mass spectrometry to identify the tryptic peptides of the protein spots and 2) isolation of the trypsin-digested sample that was labeled with isotope-coded affinity tag, followed by liquid chromatography-tandem mass spectrometry for the partial separation and identification of the peptides, respectively. Functional grouping of the identified proteins indicates that the postsynaptic density is a structurally and functionally complex organelle that may be involved in a broad range of synaptic activities. These proteins include the receptors and ion channels for glutamate neurotransmission, proteins for maintenance and modulation of synaptic architecture, sorting and trafficking of membrane proteins, generation of anaerobic energy, scaffolding and signaling, local protein synthesis, and correct protein folding and breakdown of synaptic proteins. Together, these results imply that the postsynaptic density may have the ability to function (semi-) autonomously and may direct various cellular functions in order to integrate synaptic physiology.The majority of excitatory neurotransmission in the brain occurs via glutamatergic synapses. In the presynaptic element of the synapse, specialized secretion machinery determines the activity-dependent membrane fusion of glutamate-containing vesicles and the release of transmitter into the synaptic cleft. In the postsynaptic element, glutamate receptors and downstream signal transduction are organized by the protein assembly of the postsynaptic density (PSD). 1 Both the presynaptic release machinery and the PSD are electron-dense assemblies (1, 2), in which proteins are thought to be organized into distinct functional complexes (3-5) that may be dynamically regulated by neuronal activity (6 -8). The modulation of this molecular architecture of the synapse is at the basis of synaptic plasticity (6 -8), and aberrations thereof may underlie neuronal disorders.In view of the importance of the PSD in glutamatergic neurotransmission and its involvement in neuroplasticity, considerable efforts have been made to identify its protein constituents as a prelude to understand the molecular basis of PSD functioning. In the past several years, yeast two-hybrid technology has been extensively used to characterize proteins that interact with the glutamate receptors and may constitute core elements of the PSD involved in the regulation of receptor trafficking and signaling (reviewed in Refs. 9 -11). Based largely on these studies a protein-protein interaction map of the PSD has emerged. In brief, the model posits that the postsynaptic receptor complexes are localized by scaffolding proteins such as the s...

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“…Intriguingly, loss of function of either TSC1 or TSC2 trigger an enlargement of somas and dendritic spines and alter the properties of functional synapses in postmitotic hippocampal neurons (Tavazoie et al, 2005). It remains to be studied whether neuronal deregulation of TSC1/2 augment b-catenin signaling activity thus affecting neuronal plasticity, a phenomenon which is increasingly recognized to be dependent, at least in part, on the normal activity of Wnt signaling components (Salinas, 1999(Salinas, , 2005Packard et al, 2002;Wang et al, 2003;Chen et al, 2006). Third, twin and family studies have provided compelling evidence for a strong genetic component among autistic individuals (Folstein et al, 2003;Hu-Lince et al, 2005;Vorstman et al, 2006).…”

Section: Wnt Signaling and Autismmentioning

confidence: 99%

The ups and downs of Wnt signaling in prevalent neurological disorders

2006

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In order to function properly, the brain must be wired correctly during critical periods in early development. Mistakes in this process are hypothesized to occur in disorders like autism and schizophrenia. Later in life, signaling pathways are essential in maintaining proper communication between neuronal and non-neuronal cells, and disrupting this balance may result in disorders like Alzheimer's disease. The Wnt/b-catenin pathway has a well-established role in cancer. Here, we review recent evidence showing the involvement of Wnt/b-catenin signaling in neurodevelopment as well as in neurodegenerative diseases. We suggest that the onset/development of such pathological conditions may involve the additive effect of genetic variation within Wnt signaling components and of molecules that modulate the activity of this signaling cascade.

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The Drosophila Wnt, Wingless, Provides an Essential Signal for Pre- and Postsynaptic Differentiation

Cited by 386 publications

References 62 publications

An axon scaffold induced by retinal axons directs glia to destinations in theDrosophilaoptic lobe

An axon scaffold induced by retinal axons directs glia to destinations in theDrosophilaoptic lobe

Proteomics Analysis of Rat Brain Postsynaptic Density

The ups and downs of Wnt signaling in prevalent neurological disorders

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