Isoform Pattern and AChR Aggregation Activity of Agrin Expressed by Embryonic Chick Retinal Ganglion Neurons

Annies, Maik; Kröger, Stephan

doi:10.1006/mcne.2002.1125

Cited by 8 publications

(4 citation statements)

References 52 publications

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“…Fractions of GFAP/S100β‐positive astrocytes, of O4/CNPase‐positive oligodendrocytes, of fibronectin‐positive fibroblasts and of GS lectin I‐positive microglia were very low (Table 1) indicating that the procedures isolated > 99% pure populations of neurons from these regions. As expected from previous studies on rat (Barres et al 1988) and chick (Butowt et al 2000; Annies & Kroger, 2002), our preparation of mouse RGCs immunoisolated by a Thy1‐specific antibody also contained very few non‐neuronal cells (Table 1).…”

Section: Resultssupporting

confidence: 85%

Regional variations in the glial influence on synapse development in the mouse CNS

Steinmetz¹,

Buard²,

Claudepierre³

et al. 2006

The Journal of Physiology

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There is increasing evidence that synapse function depends on interactions with glial cells, namely astrocytes. Studies on specific neurons of the central nervous system (CNS) indicated that glial signals also control synapse development, but it remained unclear whether this is a general principle that applies to other neuronal cell types. To address this question, we developed new methods to immunoisolate neurons from different brain regions of postnatal mice and to culture them in a chemically defined medium. Electrophysiological recordings and immunocytochemical staining revealed vigorous synaptogenesis in hippocampal and cerebellar neurons, but not in retinal ganglion cells (RGCs) in the absence of glial cells. Co-culture with glia promoted synapse formation in RGCs as indicated by a strong increase in the incidence and frequency of action potential-independent miniature synaptic currents, but showed no such effects in hippocampal or cerebellar neurons. On the other hand, glial signals promoted the efficacy of excitatory synapses in all regions as indicated by an increase in the size of spontaneous synaptic events in cerebellar cultures and of miniature synaptic currents in hippocampal neurons and RGCs. Inhibitory synaptic currents remained largely unaffected by glia. Our results indicate that in the mammalian CNS, the way that glial signals promote the development of excitatory synapses depends on the type of neuron.

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Section: Resultssupporting

confidence: 85%

Regional variations in the glial influence on synapse development in the mouse CNS

Steinmetz¹,

Buard²,

Claudepierre³

et al. 2006

The Journal of Physiology

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“…Likewise, brains of agrin-deficient mice, whose perinatal death was prevented by the reexpression of agrin specifically in motor neurons, have a severely reduced number of pre-and postsynaptic specializations at excitatory synapses (10). In addition, agrin isoforms are highly expressed by central nervous system neurons before synapse formation, suggesting additional functions for agrin during axonal and dendritic elongation (11)(12)(13)(14)(15)(16). Although these data are consistent with a role of agrin during CNS 4 synaptogenesis, the precise role of agrin during CNS development remains to be clarified.…”

Section: Association Of Tm-agrin With Lipid Rafts Results In the Phosmentioning

confidence: 99%

“…TM-agrin is primarily expressed in the CNS on axons and dendrites during the phase of active neurite extension (15,21), and it has been hypothesized that neurite-associated TM-agrin might serve as a receptor or co-receptor (21). In agreement with this hypothesis, it was recently shown that either clustering or overexpression of TM-agrin in neurons during the phase of active neurite extension reorganizes the actin cytoskeleton and induces the rapid formation of numerous filopodia-like processes extending from the primary neurite (21,22).…”

Section: Association Of Tm-agrin With Lipid Rafts Results In the Phosmentioning

confidence: 99%

Transmembrane Form Agrin-induced Process Formation Requires Lipid Rafts and the Activation of Fyn and MAPK

Ramseger

White

Kröger

2009

Journal of Biological Chemistry

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Overexpression or clustering of the transmembrane form of the extracellular matrix heparan sulfate proteoglycan agrin (TM-agrin) induces the formation of highly dynamic filopodialike processes on axons and dendrites from central and peripheral nervous system-derived neurons. Here we show that the formation of these processes is paralleled by a partitioning of TM-agrin into lipid rafts, that lipid rafts and transmembraneagrin colocalize on the processes, that extraction of lipid rafts with methyl-␤-cyclodextrin leads to a dose-dependent reduction of process formation, that inhibition of lipid raft synthesis prevents process formation, and that the continuous presence of lipid rafts is required for the maintenance of the processes. Association of TM-agrin with lipid rafts results in the phosphorylation and activation of the Src family kinase Fyn and subsequently in the phosphorylation and activation of MAPK. Inhibition of Fyn or MAPK activation inhibits process formation. These results demonstrate that the formation of filopodia-like processes by TM-agrin is the result of the activation of a complex intracellular signaling cascade, supporting the hypothesis that TM-agrin is a receptor or coreceptor on neurons.Agrin is a proteoglycan with a molecular mass of more than 500 kDa that is expressed in many tissues (for a review, see Ref. 1). Despite its widespread expression, the function of agrin is best characterized in skeletal muscle, where it is a key organizer during formation, maintenance, and regeneration of the neuromuscular junction (2, 3). Accordingly, mice with an inactivation of the agrn gene die at birth due to nonfunctional neuromuscular junctions and subsequent respiratory failure (4).Little is known about the role of agrin in other tissues, in particular in the central nervous system (for a review, see Ref. 5). Although neurons from mice with a targeted deletion of the agrn gene form synaptic specializations in vitro and in vivo (6, 7), the acute suppression of agrin expression or function by antisense probes or antibodies influences the formation and function of interneuronal synapses (8, 9). Likewise, brains of agrin-deficient mice, whose perinatal death was prevented by the reexpression of agrin specifically in motor neurons, have a severely reduced number of pre-and postsynaptic specializations at excitatory synapses (10). In addition, agrin isoforms are highly expressed by central nervous system neurons before synapse formation, suggesting additional functions for agrin during axonal and dendritic elongation (11-16). Although these data are consistent with a role of agrin during CNS 4 synaptogenesis, the precise role of agrin during CNS development remains to be clarified.Alternative first exon usage generates either a secreted soluble agrin molecule (NtA-agrin) or a transmembrane form of agrin (TM-agrin) (17, 18). The secreted form of agrin specifically interacts with the laminin ␥1-chain via its NtA-domain, resulting in a stable association with basal laminae (19,20). In contrast, in TM-agrin, t...

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“…1 Since 2000 many groups have investigated gene expression in small numbers of individual cells of the retina. 2–5…”

Section: Introductionmentioning

confidence: 99%

Building the Mega Single Cell Transcriptome Ocular Meta-Atlas

Swamy

Fufa

Hufnagel

et al. 2021

Preprint

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The development of highly scalable single cell transcriptome technology has resulted in the creation of thousands of datasets, over 30 in the retina alone. Analyzing the transcriptomes between different projects is highly desirable as this would allow for better assessment of which biological effects are consistent across independent studies. However it is difficult to compare and contrast data across different projects as there are substantial batch effects from computational processing, single cell technology utilized, and the natural biological variation. While many single cell transcriptome specific batch correction methods purport to remove the technical noise it is difficult to ascertain which method functions works best. We developed a lightweight R package (scPOP) that brings in batch integration methods and uses a simple heuristic to balance batch merging and celltype/cluster purity. We use this package along with a Snakefile based workflow system to demonstrate how to optimally merge 766,615 cells from 34 retina datsets and three species to create a massive ocular single cell transcriptome meta-atlas. This provides a model how to efficiently create meta-atlases for tissues and cells of interest.

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Isoform Pattern and AChR Aggregation Activity of Agrin Expressed by Embryonic Chick Retinal Ganglion Neurons

Cited by 8 publications

References 52 publications

Regional variations in the glial influence on synapse development in the mouse CNS

Regional variations in the glial influence on synapse development in the mouse CNS

Transmembrane Form Agrin-induced Process Formation Requires Lipid Rafts and the Activation of Fyn and MAPK

Building the Mega Single Cell Transcriptome Ocular Meta-Atlas

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