Dlg, Discs large, Discs-large, Disc large, l(1)d.lg-1
Gene model reviewed during 5.44
Stop-codon suppression (UGA) postulated; FBrf0216884.
gene_with_stop_codon_read_through ; SO:0000697
Gene model includes transcripts encoding non-overlapping portions of the full CDS.
Gene model reviewed during 5.40
Annotated transcripts do not represent all possible combinations of alternative exons and/or alternative promoters.
Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.46
5.1 (longest cDNA)
960 (aa); 102 (kD)
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\dlg1 using the Feature Mapper tool.
dlg1 has an unusual gene structure encoding isoforms with non-overlapping coding regions. Probes specific to the amino-terminal transcripts of dlg1 detect transcripts starting in embryonic stage 10 in the neurogenic region. In stage 12, expression becomes more concentrated in the ventral nerve cord and persists throughout embryogenesis.
Comment: isoform-specific expression
dlg1 is expressed in Malpighian tubule Type II (stellate) cells in early stage 13 embryos, just after they have pushed into the renal epithelium. All Malpighian tubule Type II cells contact the luminal surface of the tubules in mid stage 14 and express high levels of dlg1 as well as crb, shg, and baz.
dlg1 is expressed in central brain neuropils. Lamina cross-sections exhibited a bright ring of R1-R6 terminals that label with dlg1. Using immunoelectron microscopy, dlg1 is often seen close to the heads of the capitate projections (invaginations from surrounding epithelial glial and specialised organelles for the endocytosis of vesicle membrane), but not the stalks.
dlg1 protein is found mainly in epithelia, where it is localized at the apical part of the lateral cell membrane.
Expression of dlg1 is observed in the neuromuscular junction of wildtype fly at 3, 15, 30 and 60 days post-eclosion.
In the adult prothorax and neck, dlg1 immunoreactivity is observed in the type I boutons of motor neurons innervating ventral cervical muscles, prothoracic sternal anterior rotator muscle 31, and prothoracic sternal adductor muscle 33. dlg1 protein is localized to all prothoracic type I nerve terminals. Extrasynaptic dlg1 immunoreactivity is also observed in all adult muscles in a highly regular pattern resembling a reticular network.
In male reproductive tissue, dlg1 protein is found in the apical region of the lateral membranes of the accessory gland and the ejaculatory bulb. A complex pattern of staining is seen also in the testis. In the ovary, staining is observed in lateral membranes of follicle cells and in the cytoplasm of nurse cells and the oocyte. In cellular blastoderm embryos, dlg1 protein is found at the apical region of the forming lateral cell membrane. It is around each cell but not at the corners. At the time of dorsal closure, staining in the epidermis is restricted along the cell boundaries. Staining is seen in peripheral neurons, in gut, and in axon bundles. In larvae, dlg1 protein is found in salivary glands, proventriculus, imaginal discs, and CNS.
Comment: calyx of adult mushroom body, with localisation at the synapse
Comment: strong expression in mushroom body alpha-lobe and mushroom body alpha'-lobe
GBrowse - Visual display of RNA-Seq signalsView Dmel\dlg1 in GBrowse 2
Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
Source for identity of: dlg1 CG1725
Source for merge of: dlg1 l(1)G0276 l(1)G0456 l(1)G0342
Source for merge of: dlg1 anon- EST:Posey93
Source for merge of: dlg1 anon-WO03040301.258 anon-WO03040301.260 anon-WO03040301.268
Source for merge of: dlg1 CG1730
RNAi interference against the dlg1 S97 isoform does not result in defects in the development of the nervous system. The defects in the development of the nervous system that were reported in FBrf0159063 after injection of a dsRNA directed against the dlg1 S97 isoform were not due to an affect on the dlg1 S97 isoform, but instead were unintended off-target effects caused by a low-complexity fragment of less than 50bp at the end of the RNAi construct.
dsRNA made from templates generated with primers directed against this gene tested in RNAi screen for effects on Kc167 and S2R+ cell morphology.
The l(2)gl and dlg1 gene products regulate basal protein targeting, but not apical complex formation or spindle orientation, in both embryonic and larval neuroblasts. The l(2)gl and dlg1 proteins promote, and that of zip inhibits, actomyosin dependent basal protein targeting in neuroblasts.
The dlg1 gene product is not required for the localization of glutamate receptors at synapses.
The dlg1 product colocalises with Sh K+ channels, which are clustered at glutamatergic synapses at the larval neuromuscular junction. Results demonstrate dlg1 plays an important role in synaptic organisation in vivo that correlates with its ability to bind directly to specific membrane proteins of the synapse.
Some of the proteins of apico-lateral junctions are required both for apico-basal cell polarity and for the signalling mechanisms controlling cell proliferation, whereas others are required more specifically in cell-cell signalling.
The C-terminal sequences of Fas2 and Sh are both necessary and sufficient for targeting to the subsynaptic muscle membrane at the larval neuromuscular junction, and this localization depends on the product of dlg1.
Mutations in dlg1 can result in postsynaptic structural defects and large synaptic currents at neuromuscular junctions. Targetted expression of dlg1 using Scer\GAL4 can substantially rescue the reduced postsynaptic structure and presynaptic expression can rescue the physiological defect. Levels of postsynaptic dlg1 regulate or determine subsynaptic reticulum (SSR) size. Results suggest that dlg1 functions in the regulation of neurotransmitter release and postsynaptic structure.
The expression of dlg1 during synaptogenesis and synapse maturation has been studied.
dlg1 protein is localised on the cytoplasmic face of the septate junction and is required for the maintenance of this structure. dlg1 is also required for proper organisation of the cytoskeleton, for the differential location of membrane proteins and for apicobasal polarity of epithelial cells. These functions can be uncoupled from dlg1s role as a tumour suppressor since mutations in two domains of the protein (SH3 and GUK) cause loss of normal cell proliferation control without affecting the other functions of the protein.
Drosophila homolog of rat PSD-95.
In addition to its function as a tumor suppressor, the dlg1 gene is required for proper formation of neuromuscular synapses.
dlg1 immunoreactivity is expressed at one type of glutamatergic synapse and is associated with both presynaptic and postsynaptic membranes. Mutations in dlg1 alter the expression and cause striking changes in the structure of the subsynaptic reticulum, a postsynaptic specialisation at these synapses. Results indicate that dlg1 is required for normal synaptic structure.
Mutants display an imaginal disc neoplastic phenotype.
Endocrine mechanisms responsible for the prolongation of larval life in dlg1 mutants have been investigated: results suggest that delayed pupariation is caused by the overgrown imaginal discs inhibiting the production or release of ecdysteroids from the endocrine system.
Reduced ecdysteroid titer and delayed or blocked metamorphosis in mutants may be a result of altered neuropeptide production, which is probably secondary to the imaginal disc overgrowth.
Mutant analysis of dlg1 suggests that cell-cell interaction and communication is required for the termination of disc cell proliferation. This must occur prior to cellular response to ecdysone.
Mutations cause neoplastic imaginal overgrowth.
A protein, PSD-95, similar to the dlg1 tumour suppressor protein has been found in the rat brain. dlg1 protein is associated with septate junctions in developing flies and contains a guanylate kinase domain that is required for normal control of cell division.
Mutant analysis demonstrates that the dlg1 gene product is a guanylate kinase homolog located in a small apical belt of the lateral cell membrane coinciding in position with the septate junction.
dlg1 has been isolated and characterized.
Late larval lethal; prolonged larval stages with bloated larvae attempting pupariation around day 15; some cuticular tanning, but no adult cuticular structures formed. During early larval development, the imaginal discs are smaller than those of normal larvae of the same age and are misshapen, but as the larvae continue to survive after the normal pupariation time, the discs continue to grow. They become large, amorphous and solid, containing three times the normal numbers of cells at ten days of age; they also experience substantial cell death. By eleven days, wing and haltere discs may fuse; also first and second leg discs fuse with ventral ganglion of the CNS; great enlargement of optic lobes of brain also takes place. Discs, but not brains, transplanted into adults grow rapidly displaying invasive growth; they do not differentiate when transplanted into larvae for metamorphosis. Homozygous tissues do not survive, nor do gynandromorphs (one with male abdominal tissue vs. 66 expected). It is possible to produce homozygous germ-line clones (Perrimon, 1988). dlg1 embryos generated from such clones display defects in morphogenesis and neurogenesis; most tissues are defective; partial rescue achieved by a paternal dlg1+ contribution, in the form of either a normal X or a v+Y.