Affinage

DSCAM

Cell adhesion molecule DSCAM · UniProt O60469

Length
2012 aa
Mass
222.3 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DSCAM is a transmembrane immunoglobulin superfamily receptor that functions as a central regulator of neural circuit assembly by mediating isoform-specific homophilic binding, self-avoidance, axon guidance, and synaptic maturation. Homophilic recognition occurs through antiparallel pairing of three variable Ig domains in a double-S-shaped dimer, with massive alternative splicing generating thousands of isoforms whose diversity prevents inappropriate repulsion between neurites of different neurons while ensuring self-avoidance within individual neurons (PMID:15339666, PMID:17889655, PMID:18805093, PMID:17482551). DSCAM also serves as a netrin-1 receptor that signals through Fyn, FAK, and Pak1 to direct commissural axon guidance independently of DCC, can associate with UNC5C to mediate growth cone collapse, undergoes γ-secretase cleavage releasing a nuclear-translocating intracellular domain that regulates synapse-related gene expression, and blocks NLGN1–NRXN1β interaction to prevent premature spine maturation (PMID:18585357, PMID:22685302, PMID:30745319, PMID:34848499). Dysregulation of the DSCAM/PAK1 pathway contributes to abnormal neurogenesis in Down syndrome, and DSCAM mutations are linked to altered NMDA receptor function and autism-like behaviors (PMID:33945512, PMID:34253863).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2000 High

    The initial question of how DSCAM connects to intracellular signaling was answered by showing that Drosophila Dscam directly binds the adaptor Dock and functions in a Dock–Pak pathway for axon guidance, establishing DSCAM as an active guidance receptor rather than merely an adhesion molecule.

    Evidence Affinity purification and genetic epistasis in Drosophila Bolwig's nerve

    PMID:10892653

    Open questions at the time
    • Vertebrate signaling partners were not yet identified
    • Ligand for DSCAM unknown at this stage
  2. 2000 Medium

    The question of whether human DSCAM mediates cell–cell interactions was addressed by demonstrating cation-independent homophilic adhesion, establishing homophilic binding as a conserved property.

    Evidence Transfection into L fibroblasts and cell aggregation assay

    PMID:10925149

    Open questions at the time
    • No structural basis for homophilic binding
    • Whether binding is isoform-specific in vertebrates was untested
  3. 2004 High

    The critical question of how tens of thousands of Dscam splice isoforms achieve recognition specificity was resolved by showing that each isoform binds preferentially to itself, with specificity encoded jointly by three variable Ig domains, and that transmembrane domain variants differentially target Dscam to axons versus dendrites.

    Evidence In vitro binding assays with domain-swap experiments; transgenic rescue with GFP-fusion localization in Drosophila mushroom body neurons

    PMID:15339648 PMID:15339666

    Open questions at the time
    • Structural mechanism of isoform-specific recognition unresolved
    • Whether diversity is functionally necessary in vivo was not yet tested
  4. 2007 High

    Multiple studies converged to establish the biological function of Dscam isoform diversity: homophilic repulsion mediates dendrite self-avoidance; diversity prevents inappropriate inter-neuronal repulsion; crystal structures revealed antiparallel horseshoe dimerization through matching variable domains; and high-throughput assays confirmed >95% of ~19,000 isoforms bind homophilically.

    Evidence Single-isoform rescue in da neurons, reduced-diversity knock-in, X-ray crystallography with mutagenesis, ELISA across thousands of isoform pairs

    PMID:17481394 PMID:17482551 PMID:17721508 PMID:17851526 PMID:17889655

    Open questions at the time
    • Vertebrate Dscam lacks massive diversity; vertebrate self-avoidance mechanism was unclear
    • Signaling downstream of homophilic contact not fully delineated
  5. 2008 High

    The question of whether DSCAM has functions beyond homophilic adhesion was answered by identifying DSCAM as a netrin-1 receptor capable of mediating commissural axon attraction independently of DCC, while full-length structural analysis revealed a double-S-shaped homodimer architecture, and vertebrate Dscam was shown to direct lamina-specific synaptic targeting and self-avoidance in retina.

    Evidence Binding assays plus siRNA knockdown in chick spinal cord and Xenopus turning assay; X-ray crystallography of Dscam(1–8); loss/gain-of-function in chick and mouse retina

    PMID:18216854 PMID:18216855 PMID:18585357 PMID:18805093 PMID:18948420

    Open questions at the time
    • How netrin-1 binding and homophilic binding are coordinated on the same receptor was unknown
    • Downstream signaling from netrin–DSCAM was only partially characterized
  6. 2009 High

    DSCAM's role was extended to synaptic function and physiological circuits: it was shown to be required for synaptogenesis and postsynaptic receptor clustering in Aplysia, for respiratory circuit synchrony in mice, and netrin-1 signaling through DSCAM was shown to activate Fyn and Pak1 independently of DCC.

    Evidence Pre/postsynaptic Dscam inhibition with electrophysiology in Aplysia; Dscam-null mouse respiratory phenotype with voltage-sensitive dye imaging; siRNA/dominant-negative in chick commissural axons with phosphorylation assays

    PMID:19196994 PMID:19249274 PMID:19261893

    Open questions at the time
    • Whether DSCAM regulates mammalian synaptic receptor composition was unknown
    • Mechanism linking DSCAM to receptor clustering was not defined
  7. 2010 High

    Two advances refined DSCAM biology: Dscam1 and Dscam2 were shown to act redundantly via homophilic repulsion to ensure correct postsynaptic composition at photoreceptor synapses, and NMDA-stimulated dendritic translation of DSCAM mRNA via CPEB1 was identified as dysregulated in a Down syndrome mouse model.

    Evidence Double-mutant EM analysis at tetrad synapses; CPEB1–DSCAM mRNA immunoprecipitation with NMDA stimulation in Ts1Cje neurons

    PMID:20826308 PMID:20926679

    Open questions at the time
    • Whether translational dysregulation directly causes DS synaptic phenotypes was not tested
    • Mechanism of CPEB1-dependent translational control of DSCAM not fully elucidated
  8. 2012 High

    The signaling complexity of netrin–DSCAM was expanded by demonstrating that DSCAM associates with UNC5C in a netrin-1-stimulated manner to form a repulsive signaling complex involving FAK, Fyn, and PAK1, while DSCAM was localized to synaptic plasma membranes and shown to regulate cortical pyramidal neuron spine morphology.

    Evidence Co-IP of DSCAM–UNC5C with growth cone collapse assays and Src kinase inhibitor treatment; Dscam(del17) mutant mouse Golgi staining and subcellular fractionation

    PMID:22685302 PMID:23175819

    Open questions at the time
    • How DSCAM switches between attractive and repulsive signaling was not resolved
    • The specific spine-regulatory mechanism was unknown
  9. 2019 High

    A previously unknown signaling mode was uncovered: γ-secretase cleaves DSCAM to release its intracellular domain, which binds IPO5 and translocates to the nucleus to regulate expression of neuronal differentiation and synapse genes, establishing DSCAM as a receptor with nuclear signaling capacity.

    Evidence ORFeome screen, direct ICD–IPO5 binding, γ-secretase inhibitor, nuclear fractionation, RNA-seq, and synapse quantification in hippocampal neurons

    PMID:30745319

    Open questions at the time
    • Nuclear targets and transcriptional partners of the ICD were not fully defined
    • Whether ICD nuclear signaling occurs in vivo during development was not shown
  10. 2020 High

    DSCAM's role in cortical neurogenesis was established by showing it suppresses the RapGEF2–Rap1–N-cadherin cascade at apical endfeet to control neuronal delamination, revealing a non-canonical adhesion-regulatory function distinct from self-avoidance.

    Evidence Dscam knockdown with Cre-loxP labeling, co-IP of DSCAM–RapGEF2, epistasis rescue by co-knockdown of RapGEF2 or N-cadherin

    PMID:32917586

    Open questions at the time
    • Whether DSCAM directly inhibits RapGEF2 GEF activity or sequesters it was not distinguished
    • Relevance to human cortical development not tested
  11. 2021 High

    Three studies converged to link DSCAM dysfunction to neurodevelopmental disease mechanisms: DSCAM's extracellular domain blocks NLGN1–NRXN1β interaction to prevent premature spine maturation (with DSCAM-deficient mice showing autism-like behavior); DSCAM mutation in an ASD patient reduces NMDA receptor expression and currents; and DSCAM/PAK1 pathway suppression rescues abnormal neurogenesis in Down syndrome organoids.

    Evidence Competitive binding assay for NLGN1–NRXN1β, KO electrophysiology and behavior; patient iPSC-derived neurons with rescue; CRISPR/CRISPRi in DS iPSC organoids with scRNA-seq

    PMID:33945512 PMID:34253863 PMID:34848499

    Open questions at the time
    • Relative contributions of DSCAM overexpression versus other trisomy 21 genes to DS brain phenotypes are not isolated
    • Whether NLGN1 interaction and NMDA-R regulation are mechanistically linked is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how DSCAM coordinates its multiple functions (homophilic self-avoidance, netrin attraction/repulsion, NLGN1 regulation, nuclear signaling) through a single receptor, and what structural or post-translational switches determine context-dependent signaling output.
  • No integrated structural model of DSCAM engaging multiple ligands/co-receptors simultaneously
  • Relative physiological importance of γ-secretase cleavage versus full-length receptor signaling in vivo is untested
  • Vertebrate DSCAM self-avoidance mechanism with limited isoform diversity remains poorly understood

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 7 GO:0060089 molecular transducer activity 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 7 R-HSA-162582 Signal Transduction 6 R-HSA-112316 Neuronal System 3 R-HSA-1500931 Cell-Cell communication 3
Partners
DOCK1IPO5NLGN1NTN1PAK1RAPGEF2TBCDUNC5C

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Drosophila Dscam binds directly to both the SH2 and SH3 domains of the adaptor protein Dock, and genetic studies showed that Dscam, Dock, and Pak act together in the same pathway to direct axon pathfinding of Bolwig's nerve to an intermediate target. Affinity purification, direct binding assay (SH2/SH3 domain binding), genetic epistasis Cell High 10892653
2000 Human DSCAM mediates cation-independent homophilic intercellular adhesion; DSCAM-expressing L cells aggregate with faster kinetics and in a homophilic manner. Transfection of human DSCAM into mouse L fibroblasts, cell aggregation assay, Western blot Brain research. Molecular brain research Medium 10925149
2004 Different Dscam isoforms exhibit isoform-specific homophilic binding: each isoform binds to itself but not (or poorly) to other isoforms, and the amino acid sequences of all three variable Ig domains (encoded by exons 4, 6, and 9) jointly determine binding specificity. In vitro binding assays with recombinant Dscam isoforms, domain-swap experiments Cell High 15339666
2004 The transmembrane/juxtamembrane segment encoded by exon 17.2 targets Dscam to axons, while exon 17.1-containing Dscam is targeted to dendrites; differential subcellular targeting underlies distinct roles in axon vs. dendrite morphogenesis in mushroom body neurons. Transgenic rescue experiments, GFP-fusion protein subcellular localization in Drosophila neurons Neuron High 15339648
2004 Human DSCAM directly binds Pak1 and stimulates Pak1 phosphorylation and kinase activity; DSCAM also activates JNK and p38 MAP kinases, and expression of the DSCAM cytoplasmic domain induces JNK-dependent morphological changes. Co-immunoprecipitation, in vitro kinase assay, dominant-negative expression in cultured cells The Journal of biological chemistry Medium 15169762
2005 Mutually exclusive splicing of Dscam exon 6 (48 variants) is directed by competing RNA secondary structures: a docking site in the intron downstream of exon 5 pairs with selector sequences upstream of each exon 6 variant, juxtaposing only one exon at a time to the upstream constitutive exon. Identification of conserved intronic elements, RNA secondary structure analysis, mutational analysis Cell High 16213213
2007 Dscam mediates dendrite self-avoidance in Drosophila da sensory neurons through isoform-specific homophilic interactions on the cell surface, while the cytoplasmic tail converts recognition to repulsion; diversity of isoforms prevents inappropriate repulsion between dendrites of different neurons sharing the same receptive field. Genetic loss-of-function, single-isoform rescue transgenes, live imaging of dendrite self-avoidance Cell High 17482551
2007 A single Dscam isoform introduced into Dscam-mutant da neurons significantly restores dendrite self-avoidance; expression of a common isoform across different neuronal classes causes their dendrites to repel each other, demonstrating that isoform diversity is necessary to allow coexistence of dendrites from different neuronal classes. Dscam mutant rescue with defined single isoforms, mosaic analysis, live imaging Neuron High 17481394
2007 X-ray crystal structures of two Dscam isoforms reveal a horseshoe configuration; homodimerization couples variable domain D2 with D2 and D3 with D3 in an antiparallel fashion; structure-guided mutagenesis confirms that epitope I (variable residues of D2) confers isoform-specific homophilic binding specificity. X-ray crystallography, structure-guided mutagenesis, domain-swap experiments Nature High 17721508
2007 High-throughput ELISA-based binding assays show that >95% of the 19,008 Dscam ectodomain isoforms exhibit isoform-specific homophilic binding; each variable domain binds its identical counterpart in an opposing isoform independently. High-throughput ELISA-based binding assay across thousands of isoform pairs Cell High 17889655
2007 Reduction of the Dscam ectodomain repertoire to a single isoform via homologous recombination severely disorganizes neural circuits; neurons must express distinct isoforms from their neighbors for proper wiring, but the specific identity of the isoform is unimportant. Homologous recombination to reduce ectodomain diversity, genetic mosaic analysis Nature High 17851526
2007 Dscam juxtamembrane variant TM2 (exon 17.2) is required for postembryonic axon arborization, while TM1 (exon 17.1) primarily regulates dendritic elaboration; the juxtamembrane regions govern axonal vs. dendritic targeting of the Dscam protein. miRNA-based RNAi to selectively knock down TM1 or TM2 variants, transgenic rescue, subcellular localization The Journal of neuroscience High 17581959
2008 DSCAM is a netrin-1 receptor expressed on spinal commissural axons; it binds netrin-1 and is necessary for commissural axon growth toward and across the midline; Xenopus neurons expressing DSCAM can be attracted by netrin-1 independently of DCC. Binding assays (netrin-1 – DSCAM interaction), siRNA knockdown in chick spinal cord, Xenopus turning assay Cell High 18585357
2008 The crystal structure of Dscam(1–8) reveals that the homophilic binding region adopts a double-S-shaped homodimer; in this conformation all three pairs of variable domains match in an antiparallel fashion; constant domain intramolecular interactions also promote homophilic binding. X-ray crystallography of Dscam(1–8), mutagenesis, biochemical binding assays Cell High 18805093
2008 Vertebrate Dscam and DscamL mediate homophilic adhesion and direct lamina-specific synaptic connections in chick retina; loss- and gain-of-function show these IgSF members determine which IPL sublaminae synaptic partners arborize in. In vivo loss- and gain-of-function in chick retina, homophilic adhesion assays, immunolocalization Nature High 18216854
2008 Mouse DSCAM mediates isoneuronal self-avoidance for process arborization and heteroneuronal self-avoidance within specific amacrine cell types; loss of DSCAM causes hyperfasciculated processes and clumped cell bodies rather than regular mosaic spacing. Analysis of spontaneous Dscam mutant mice, immunohistochemistry, mosaic analysis Nature High 18216855
2008 Dscam guides embryonic axons in Drosophila through both Netrin-dependent and Netrin-independent functions; cell overlay assays show Netrin binds to both fly and vertebrate Dscam with the same affinity as DCC; simultaneous knockout of Dscam, Dscam3, and fra produces stronger midline crossing defects than Netrin removal alone. Cell overlay binding assays, genetic double/triple mutant analysis, overexpression-induced ectopic midline crossing Development High 18948420
2009 DSCAM is expressed on commissural axons, interacts with Netrin-1, and mediates netrin-induced axon outgrowth and commissural axon turning; DSCAM activates Fyn and Pak1 phosphorylation independently of DCC in transfected cells. siRNA knockdown in ovo, dominant-negative overexpression, co-immunoprecipitation, phosphorylation assays in transfected cells Proceedings of the National Academy of Sciences of the United States of America High 19196994
2009 In Aplysia, Dscam is required pre- and postsynaptically for de novo synaptogenesis and for clustering of postsynaptic AMPA-like receptors; Dscam-mediated transsynaptic interactions are also reactivated during learning-related synapse formation to remodel both AMPA-like and NMDA-like receptors. Inhibition of Dscam pre- or postsynaptically in Aplysia neuronal cultures, electrophysiology, receptor clustering assays Neuron High 19249274
2009 Mouse DSCAM and DSCAML1 function in dendritic self-avoidance in multiple retinal cell types (RGCs, rod bipolar cells, AII amacrine cells), but are not essential for synaptic specificity or laminar stratification in the mouse retina. Analysis of Dscam-/- and Dscaml1-/- mice, immunohistochemistry, electrophysiology of rod circuit Neuron High 19945391
2009 Mouse DSCAM is required for synchroneity of pre-inspiratory neurons in the rostral ventrolateral medulla; Dscam-null mice die within 24 h after birth from irregular respiration, and optical imaging reveals loss of pre-inspiratory neuron synchrony. Dscam knockout mice, plethysmography, medulla-spinal cord preparation, voltage-sensitive dye imaging The Journal of neuroscience High 19261893
2001 DSH3PX1 (a sorting nexin/Dscam complex component) co-immunoprecipitates with Dock and Dscam from S2 cells and interacts with Drosophila Wasp (actin polymerization machinery) and AP-50 (clathrin adaptor), placing Dscam in a complex linking it to cytoskeletal rearrangements and receptor trafficking. Affinity purification, co-immunoprecipitation, domain-interaction mapping The Journal of biological chemistry Medium 11546816
2010 NMDA stimulation rapidly induces dendritic translation of DSCAM mRNA in wild-type mouse hippocampal neurons; DSCAM mRNA localizes to dendrites and associates with CPEB1; this NMDA-mediated translational regulation is lost in Ts1Cje (Down syndrome model) neurons. Dendritic fractionation, RNA immunoprecipitation (CPEB1-DSCAM mRNA), NMDA stimulation with protein level measurements, Ts1Cje mouse model The Journal of neuroscience Medium 20926679
2012 DSCAM associates with UNC5C and this interaction is stimulated by netrin-1; DSCAM co-localizes with UNC5C in neurons; knockdown of DSCAM or UNC5C suppresses netrin-1-induced growth cone collapse; netrin-1 increases tyrosine phosphorylation of DSCAM, UNC5C, FAK, Fyn, and PAK1 and promotes their complex formation, dependent on Src family kinase activity. Co-immunoprecipitation, shRNA knockdown, dominant-negative overexpression, growth cone collapse assay, phosphorylation assays, Src kinase inhibitor treatment The Journal of biological chemistry High 22685302
2012 Mouse DSCAM contributes to dendrite arborization and spine formation in cortical pyramidal neurons; DSCAM localizes to synaptic plasma membranes; DSCAM(del17) mutants show transient defects in layer V pyramidal neuron dendrite branching and lasting changes in spine morphology (decreased large stable spines, increased small immature spines). Immunofluorescence subcellular fractionation, analysis of Dscam(del17) mutant mice, Golgi staining of dendrites and spines The Journal of neuroscience Medium 23175819
2015 Tubulin folding cofactor D (TBCD) physically interacts with the intracellular domain of Dscam, and genetic analyses show TBCD cooperates with Dscam in vivo for neuronal morphogenesis; disruption of microtubules by TBCD mutation phenocopies Dscam-related dendritic arborization defects. Co-immunoprecipitation (TBCD–Dscam intracellular domain), genetic epistasis in Drosophila projection neurons, live imaging The Journal of neuroscience Medium 25653356
2015 Gain-of-function DSCAM in mouse retina is sufficient to drive cell death and to retarget neurites; DSCAM is necessary for precise dendrite lamination and restricts the stratum in which exploring retinal dendrites stabilize in a dosage-dependent manner. Gain-of-function mouse allele, loss-of-function mouse allele, conditional deletion, immunohistochemistry The Journal of neuroscience Medium 25855178
2015 Dysregulated Dscam levels enlarge presynaptic arbors in Drosophila, and this cellular defect can be ameliorated by genetic and pharmacological inhibition of Abelson kinase (Abl), placing Abl downstream of dysregulated Dscam. Genetic overexpression of Dscam, Abl inhibitor treatment, genetic epistasis (Abl mutants suppress Dscam overexpression phenotype) eLife Medium 25988807
2016 Dscam2 directs dendritic targeting of lamina neuron L4 through homophilic adhesion (not repulsion); Dscam4 acts in the same pathway as Dscam2 for L4 targeting, and together they ensure tiling through heterotypic interactions. Genetic mosaics, conditional loss-of-function, live imaging of dendritic targeting Neuron Medium 26844831
2019 The intracellular domain (ICD) of DSCAM interacts with IPO5 (importin beta family) via a conserved nuclear localization signal; the DSCAM ICD is released by γ-secretase-dependent cleavage and translocates to the nucleus, where it alters expression of genes associated with neuronal differentiation, apoptosis, and synapse formation; increased DSCAM or DSCAM ICD levels decrease synapse number in hippocampal neurons. High-throughput ORFeome screen, direct binding assay (ICD–IPO5), γ-secretase inhibitor, nuclear fractionation, RNA-seq, synapse number quantification in primary neurons The EMBO journal High 30745319
2020 DSCAM controls neuronal delamination by locally suppressing the RapGEF2–Rap1–N-cadherin cascade at the apical endfeet in the dorsal midbrain; DSCAM associates with RapGEF2 to inactivate Rap1, thereby reducing N-cadherin membrane localization and ventricular attachment; co-knockdown of RapGEF2 or N-cadherin rescues the endfeet detachment defect caused by Dscam knockdown. Cre-loxP-based neuronal labeling, Dscam knockdown, co-immunoprecipitation (DSCAM–RapGEF2), N-cadherin localization assays, epistasis rescue experiments Science advances High 32917586
2021 DSCAM deficiency causes accelerated dendritic spine maturation; the extracellular domain of DSCAM interacts with neuroligin-1 (NLGN1) to block the NLGN1–neurexin1β interaction; DSCAM extracellular domain can rescue spine over-maturation in DSCAM-knockdown neurons; DSCAM-deficient mice show increased glutamatergic transmission and autism-like behaviors. Co-immunoprecipitation (DSCAM–NLGN1), competitive binding assay (NLGN1–NRXN1β), DSCAM KD and KO in pyramidal neurons, electrophysiology, behavioral assays The Journal of neuroscience High 34848499
2021 Suppression of the DSCAM/PAK1 pathway (using CRISPR/Cas9, CRISPRi, or small-molecule inhibitors) reverses abnormal neurogenesis in cerebral organoids derived from Down syndrome iPSCs, directly linking dysregulation of the DSCAM/PAK1 signaling pathway to developmental brain defects in DS. iPSC-derived cerebral organoids, CRISPR/Cas9, CRISPRi, small-molecule inhibitors, scRNA-seq, histology The Journal of clinical investigation High 33945512
2021 DSCAM co-localizes with NMDA receptor components in dendritic spines; DSCAM mutation causes downregulation of NMDA-R subunit expression and reduced NMDA-R-mediated currents; wild-type DSCAM rescue restores normal NMDA-R currents; DSCAM KD reduces NMDA-R subunit levels rescued by shRNA-resistant DSCAM. iPSC-derived neurons from ASD patient with DSCAM mutation, electrophysiology, shRNA knockdown, rescue with WT or truncated DSCAM, co-localization imaging Molecular psychiatry High 34253863
2010 Drosophila Dscam1 and Dscam2, acting redundantly through homophilic repulsion, ensure the invariable combination of L1 and L2 postsynaptic elements at photoreceptor tetrad synapses; loss of both proteins allows elements from the same cell to incorporate into the same postsynaptic tetrad. Dscam1;Dscam2 double mutant analysis, electron microscopy of tetrad synapses Neuron High 20826308
2017 DSCAM is required for fasciculation and growth of RGC axons in the embryonic mouse optic pathway; gain of DSCAM function produces exuberant growth; in vitro DSCAM promotes RGC axon growth and fasciculation independently of cell contact; both axonal and environmental DSCAM are required, consistent with a homotypic mode of action. Dscam mutant mice, DSCAM gain-of-function mice, in vitro axon growth assays, in vivo timing of axon arrival at dorsal thalamus Proceedings of the National Academy of Sciences of the United States of America High 28137836
2009 Endodomain diversity in Drosophila Dscam (including or excluding exons 19 and 23) is developmentally regulated; exon 19-containing Dscam governs embryonic neuronal wiring while Dscam lacking exon 19 is more efficiently targeted to neurites and more potently suppresses axon bifurcation postembryonically. Stage-specific isoform expression analysis, transgenic rescue with defined endodomain isoforms, subcellular targeting assays The Journal of neuroscience Medium 19211897

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity. Cell 806 10892653
2008 Dscam and Sidekick proteins direct lamina-specific synaptic connections in vertebrate retina. Nature 309 18216854
2007 Dendrite self-avoidance is controlled by Dscam. Cell 288 17482551
2004 Alternative splicing of Drosophila Dscam generates axon guidance receptors that exhibit isoform-specific homophilic binding. Cell 261 15339666
2008 Neurite arborization and mosaic spacing in the mouse retina require DSCAM. Nature 224 18216855
1998 DSCAM: a novel member of the immunoglobulin superfamily maps in a Down syndrome region and is involved in the development of the nervous system. Human molecular genetics 222 9426258
2007 Drosophila sensory neurons require Dscam for dendritic self-avoidance and proper dendritic field organization. Neuron 219 17481394
2008 DSCAM is a netrin receptor that collaborates with DCC in mediating turning responses to netrin-1. Cell 212 18585357
2005 Mutually exclusive splicing of the insect Dscam pre-mRNA directed by competing intronic RNA secondary structures. Cell 206 16213213
2004 Stochastic yet biased expression of multiple Dscam splice variants by individual cells. Nature genetics 199 14758360
2009 DSCAM and DSCAML1 function in self-avoidance in multiple cell types in the developing mouse retina. Neuron 194 19945391
2016 The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression. Nature communications 191 27666543
2007 A vast repertoire of Dscam binding specificities arises from modular interactions of variable Ig domains. Cell 189 17889655
2004 Analysis of Dscam diversity in regulating axon guidance in Drosophila mushroom bodies. Neuron 181 15339649
2007 Dscam diversity is essential for neuronal wiring and self-recognition. Nature 173 17851526
2003 Axonal targeting of olfactory receptor neurons in Drosophila is controlled by Dscam. Neuron 173 12546818
2002 Drosophila Dscam is required for divergent segregation of sister branches and suppresses ectopic bifurcation of axons. Neuron 172 11856530
2008 Dscam-mediated cell recognition regulates neural circuit formation. Annual review of cell and developmental biology 159 18837673
2006 The molecular diversity of Dscam is functionally required for neuronal wiring specificity in Drosophila. Cell 153 16678102
2004 Transmembrane/juxtamembrane domain-dependent Dscam distribution and function during mushroom body neuronal morphogenesis. Neuron 143 15339648
2009 DSCAM functions as a netrin receptor in commissural axon pathfinding. Proceedings of the National Academy of Sciences of the United States of America 137 19196994
2009 Dscam and DSCAM: complex genes in simple animals, complex animals yet simple genes. Genes & development 135 19171779
2006 Dendritic patterning by Dscam and synaptic partner matching in the Drosophila antennal lobe. Nature neuroscience 133 16474389
2007 Structural basis of Dscam isoform specificity. Nature 128 17721508
2021 DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome. The Journal of clinical investigation 104 33945512
2008 Dscam guides embryonic axons by Netrin-dependent and -independent functions. Development (Cambridge, England) 104 18948420
2008 A double S shape provides the structural basis for the extraordinary binding specificity of Dscam isoforms. Cell 92 18805093
2011 Bacteria-Induced Dscam Isoforms of the Crustacean, Pacifastacus leniusculus. PLoS pathogens 85 21695245
2007 A regulator of Dscam mutually exclusive splicing fidelity. Nature structural & molecular biology 85 21188797
2011 Over-expression of DSCAM and COL6A2 cooperatively generates congenital heart defects. PLoS genetics 75 22072978
2009 Dscam mediates remodeling of glutamate receptors in Aplysia during de novo and learning-related synapse formation. Neuron 75 19249274
2001 Alternative splicing of the Drosophila Dscam pre-mRNA is both temporally and spatially regulated. Genetics 74 11606537
2010 NMDA-mediated regulation of DSCAM dendritic local translation is lost in a mouse model of Down's syndrome. The Journal of neuroscience : the official journal of the Society for Neuroscience 71 20926679
2009 The putative invertebrate adaptive immune protein Litopenaeus vannamei Dscam (LvDscam) is the first reported Dscam to lack a transmembrane domain and cytoplasmic tail. Developmental and comparative immunology 68 19635499
2018 DSCAM-AS1 promotes tumor growth of breast cancer by reducing miR-204-5p and up-regulating RRM2. Molecular carcinogenesis 67 30457164
2012 Down syndrome cell adhesion molecule (DSCAM) associates with uncoordinated-5C (UNC5C) in netrin-1-mediated growth cone collapse. The Journal of biological chemistry 65 22685302
2010 Drosophila dscam proteins regulate postsynaptic specificity at multiple-contact synapses. Neuron 65 20826308
2000 Down syndrome cell adhesion molecule DSCAM mediates homophilic intercellular adhesion. Brain research. Molecular brain research 64 10925149
2014 Dscam and pancrustacean immune memory - a review of the evidence. Developmental and comparative immunology 63 24657209
2018 Pathogen-Specific Binding Soluble Down Syndrome Cell Adhesion Molecule (Dscam) Regulates Phagocytosis via Membrane-Bound Dscam in Crab. Frontiers in immunology 61 29720978
2018 LncRNA DSCAM-AS1 acts as a sponge of miR-137 to enhance Tamoxifen resistance in breast cancer. Journal of cellular physiology 60 30203615
2001 Cloning and functional characterization of DSCAML1, a novel DSCAM-like cell adhesion molecule that mediates homophilic intercellular adhesion. Biochemical and biophysical research communications 60 11453658
2001 The sorting nexin, DSH3PX1, connects the axonal guidance receptor, Dscam, to the actin cytoskeleton. The Journal of biological chemistry 60 11546816
2013 Ultra-deep profiling of alternatively spliced Drosophila Dscam isoforms by circularization-assisted multi-segment sequencing. The EMBO journal 56 23792425
2012 DSCAM contributes to dendrite arborization and spine formation in the developing cerebral cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 56 23175819
2006 Got diversity? Wiring the fly brain with Dscam. Trends in biochemical sciences 56 16919957
2014 Review of Dscam-mediated immunity in shrimp and other arthropods. Developmental and comparative immunology 54 24727482
2009 Endodomain diversity in the Drosophila Dscam and its roles in neuronal morphogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 54 19211897
2010 Competing RNA secondary structures are required for mutually exclusive splicing of the Dscam exon 6 cluster. RNA (New York, N.Y.) 51 21159795
2011 Penaeus monodon Dscam (PmDscam) has a highly diverse cytoplasmic tail and is the first membrane-bound shrimp Dscam to be reported. Fish & shellfish immunology 49 21338689
2008 Dscam-mediated repulsion controls tiling and self-avoidance. Current opinion in neurobiology 49 18538559
2017 DSCAM promotes axon fasciculation and growth in the developing optic pathway. Proceedings of the National Academy of Sciences of the United States of America 48 28137836
2019 Nuclear import of the DSCAM-cytoplasmic domain drives signaling capable of inhibiting synapse formation. The EMBO journal 46 30745319
2013 Immunoglobulin superfamily protein Dscam exhibited molecular diversity by alternative splicing in hemocytes of crustacean, Eriocheir sinensis. Fish & shellfish immunology 46 23856639
2011 Alternative splicing of the Anopheles gambiae Dscam gene in diverse Plasmodium falciparum infections. Malaria journal 46 21651790
2001 DSCAM, a highly conserved gene in mammals, expressed in differentiating mouse brain. Biochemical and biophysical research communications 44 11237714
2020 Long non-coding RNA DSCAM-AS1 contributes to the tumorigenesis of cervical cancer by targeting miR-877-5p/ATXN7L3 axis. Bioscience reports 43 31737900
2015 DSCAM promotes refinement in the mouse retina through cell death and restriction of exploring dendrites. The Journal of neuroscience : the official journal of the Society for Neuroscience 43 25855178
2012 The evolution of Dscam genes across the arthropods. BMC evolutionary biology 43 22500922
2005 The iStem, a long-range RNA secondary structure element required for efficient exon inclusion in the Drosophila Dscam pre-mRNA. Molecular and cellular biology 43 16287842
2016 Dscam Proteins Direct Dendritic Targeting through Adhesion. Neuron 42 26844831
2004 The Down syndrome cell adhesion molecule (DSCAM) interacts with and activates Pak. The Journal of biological chemistry 42 15169762
2011 Cell autonomy of DSCAM function in retinal development. Developmental biology 41 22063212
2006 Tracking the evolution of alternatively spliced exons within the Dscam family. BMC evolutionary biology 41 16483367
2012 Genetic analysis of DSCAM's role as a Netrin-1 receptor in vertebrates. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 22238077
2019 Dscam in immunity: A question of diversity in insects and crustaceans. Developmental and comparative immunology 39 31734281
2013 Properties of Litopenaeus vannamei Dscam (LvDscam) isoforms related to specific pathogen recognition. Fish & shellfish immunology 39 23932986
2012 Shrimp Dscam and its cytoplasmic tail splicing activator serine/arginine (SR)-rich protein B52 were both induced after white spot syndrome virus challenge. Fish & shellfish immunology 39 23123640
2010 A novel null allele of mouse DSCAM survives to adulthood on an inbred C3H background with reduced phenotypic variability. Genesis (New York, N.Y. : 2000) 39 20715164
2007 Specific Drosophila Dscam juxtamembrane variants control dendritic elaboration and axonal arborization. The Journal of neuroscience : the official journal of the Society for Neuroscience 39 17581959
2019 Alternatively spliced down syndrome cell adhesion molecule (Dscam) controls innate immunity in crab. The Journal of biological chemistry 38 31537644
2009 DSCAM deficiency causes loss of pre-inspiratory neuron synchroneity and perinatal death. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 19261893
2020 Up-Regulation of FSTL3, Regulated by lncRNA DSCAM-AS1/miR-122-5p Axis, Promotes Proliferation and Migration of Non-Small Cell Lung Cancer Cells. OncoTargets and therapy 35 32280246
2009 Massive expansions of Dscam splicing diversity via staggered homologous recombination during arthropod evolution. RNA (New York, N.Y.) 35 19934230
2007 Molecular diversity of Dscam: recognition of molecular identity in neuronal wiring. Nature reviews. Neuroscience 35 18026165
2012 Neuronal clustering and fasciculation phenotype in Dscam- and Bax-deficient mouse retinas. The Journal of comparative neurology 34 22396220
2012 An RNA architectural locus control region involved in Dscam mutually exclusive splicing. Nature communications 34 23212384
2015 Linking cell surface receptors to microtubules: tubulin folding cofactor D mediates Dscam functions during neuronal morphogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 29 25653356
2016 A large family of Dscam genes with tandemly arrayed 5' cassettes in Chelicerata. Nature communications 28 27080167
2015 Dysregulated Dscam levels act through Abelson tyrosine kinase to enlarge presynaptic arbors. eLife 28 25988807
2021 DSCAM Deficiency Leads to Premature Spine Maturation and Autism-like Behaviors. The Journal of neuroscience : the official journal of the Society for Neuroscience 27 34848499
2020 DSCAM-AS1-Driven Proliferation of Breast Cancer Cells Involves Regulation of Alternative Exon Splicing and 3'-End Usage. Cancers 27 32503257
2019 Long noncoding RNA DSCAM-AS1 functions as an oncogene in non-small cell lung cancer by targeting BCL11A. European review for medical and pharmacological sciences 27 30779076
2019 Long non-coding RNA DSCAM-AS1 accelerates the progression of hepatocellular carcinoma via sponging miR-338-3p. American journal of translational research 27 31396335
2014 DSCAM and DSCAML1 regulate the radial migration and callosal projection in developing cerebral cortex. Brain research 27 25451118
2012 A novel mouse Dscam mutation inhibits localization and shedding of DSCAM. PloS one 27 23300735
2014 WSSV-induced crayfish Dscam shows durable immune behavior. Fish & shellfish immunology 26 24973514
2020 DSCAM regulates delamination of neurons in the developing midbrain. Science advances 25 32917586
2011 Dscam mutation leads to hydrocephalus and decreased motor function. Protein & cell 25 21904980
2017 DSCAM-mediated control of dendritic and axonal arbor outgrowth enforces tiling and inhibits synaptic plasticity. Proceedings of the National Academy of Sciences of the United States of America 24 29114051
2014 DSCAM localization and function at the mouse cone synapse. The Journal of comparative neurology 24 24477985
2001 Dscam is associated with axonal and dendritic features of neuronal cells. Journal of neuroscience research 24 11746351
2020 LncRNA DSCAM-AS1 promotes colorectal cancer progression by acting as a molecular sponge of miR-384 to modulate AKT3 expression. Aging 23 32453706
2018 DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiring. Neural development 23 30219101
2020 Long non-coding RNA DSCAM-AS1 upregulates USP47 expression through sponging miR-101-3p to accelerate osteosarcoma progression. Biochemistry and cell biology = Biochimie et biologie cellulaire 22 32379981
2017 Characterize a typically Dscam with alternative splicing in mud crab Scylla paramamosain. Fish & shellfish immunology 22 29042325
2021 Dysfunction of NMDA receptors in neuronal models of an autism spectrum disorder patient with a DSCAM mutation and in Dscam-knockout mice. Molecular psychiatry 21 34253863
2020 Long Noncoding RNA DSCAM-AS1 Facilitates Colorectal Cancer Cell Proliferation and Migration via miR-137/Notch1 Axis. Journal of Cancer 21 33046983
2014 Roles for DSCAM and DSCAML1 in central nervous system development and disease. Advances in neurobiology 21 25300140
2021 A Review on the Carcinogenic Roles of DSCAM-AS1. Frontiers in cell and developmental biology 20 34708048