PDE4, EG:140G11.4 , fs(1)M42, EG:96G10.7
Annotated transcripts do not represent all supported alternative splices within 5' UTR.
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
A non-AUG start codon may be used for translation of one or more transcripts of this gene; based on the presence of conserved protein signatures within the 5' UTR without an in-frame AUG (FBrf0243886).
777, 714, 702, 628 (aa); 85, 79, 77, 71 (kD predicted)
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\dnc using the Feature Mapper tool.
Immunolocalization of dnc protein to thin sections of adult brain shows that it is largely concentrated in the mushroom bodies. Within mushroom bodies, the γ lobes stain more intensely than the α or β lobes, peduncle staining intensity varies with position and calyx expression is uniform. An intermediate level of staining is seen in most neuropil structures including the inner optic lobe neuropil, protocerebrum, suboesophageal ganglion, antennal lobes, and central complex. A conspicuous lack of staining is found in the photoreceptor cell layer, lamina, antennal nerve, and median bundle. Staining was also observed in the neuropil of thoracic and abdominal ganglia. Intense staining was observed in larval mushroom body neuropil. In contrast to adult brain, some cell body staining was observed in the larval mushroom body.
GBrowse - Visual display of RNA-Seq signalsView Dmel\dnc in GBrowse 2
The interval between sam and dnc is that between sam2 (rightmost allele of sam in this study) and dncM11 (leftmost allele of dnc in this study). dncM11 is 0.04 +/- 0.01cM to the left of a cluster of dnc mutations (dncM14, dncML, dnc1 and dnc2). The interval between dnc and cff is that between dnc1 and cff1.
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.
dsRNA made from templates generated with primers directed against this gene tested in RNAi screen for effects on Kc167 and S2R+ cell morphology.
dnc mutant larval neurons lack a maintained outward current component that is down-regulated by cAMP.
Subsets of dnc and rut neurons display abnormal spontaneous spikes and altered firing patterns in 'giant' neuron cultures. Abnormal spike activity and reduced K+ current remain in dnc rut double mutants suggesting that the opposite effects on cAMP metabolism by dnc and rut do not counterbalance the mutual functional defects. The aberrant spontaneous activity and altered frequency coding in different stimulus paradigms may present problems in the stability and reliability of neural circuits for information processing during certain behavioural tasks, raising the possibility of modulation in neuronal excitability as a cellular mechanisms underlying learning and memory.
Mutations of dnc affect habituation of the electrically stimulated giant fibre response.
Phenotypic analysis reveals control of growth cone mobility requires optimal cAMP levels within an operational range.
At temperatures ranging from 20oC to 37.5oC temperature sensitive mutants exhibit no effect on the heart rate of larvae.
SP injection into dnc mutant females fails to elicit the usual SP response of increased oviposition and decreased receptivity to males.
Injection of Acp70A into mutant virgin females fails to elicit any response in behaviour.
Mutation of dnc is associated with an abnormal pacemaker resetting response and a shortening of circadian period. Mutations selectively alter phase delays with no apparent effects on phase advances of the pacemaker.
dnc gene product is preferentially expressed in the mushroom bodies. Cell specific ablation of the mushroom bodies, by hydroxyurea, demonstrates they mediate associative odour learning in flies.
P-element mediated introduction of dnc and rat dnc into dnc mutants allows some phenotype rescue and supports the physiological role of the dnc gene product during memory and learning acquisition as opposed to a purely developmental defect as the cause of the dnc phenotype. Rat dnc is capable of partially replacing the function of dnc.
The relationship between structural complexity and functional diversity of the dnc gene has been investigated using the many chromosomal rearrangements in the dnc region. Transcription start sites 4 and 5 are required for female fertility. Transcription start site 3 is important for elevated dnc expression in the mushroom bodies and normal 90 minute memory. Transcription start site 4 is required for general neuropil expression and for normal initial learning.
Behavioural experiments reveal interesting functional properties of the dnc gene that have eluded molecular and biochemical analyses.
Two electrode voltage clamping studies of third-instar larval muscle, with and without K+-channel blockers suggests that a specific K+ channel conductance might be relevant to the lack of synaptic plasticity at the dnc neuromuscular synapse.
dnc plays a major role in the maternal regulation of embryonic cAMP content.
dnc mutant analysis suggests that the cAMP cascade plays a role in the shaping neuronal connectivity.
In dnc mutants a K+ selective channel, that is activated directly and reversibly by cAMP, has a much higher probability of opening compared to wild type.
dnc phosphodiesterase (PDE) localization has been determined by antibody staining. Results demonstrate that dnc PDE is very concentrated in the neuropil associated with the mushroom body cells.
dnc is structurally complex gene with multiple RNAs exhibiting a heterogeneity of dnc transcripts that result from transcription initiation at multiple sites, alternative splicing and processes that generate different 3' ends.
dnc mutants are defective in a step of the cAMP cascade: they show impaired synaptic facilitation and post-tetanic potentiation as well as abnormal responses to direct application of dibutyryl cAMP. Results suggest that the cAMP cascade plays a role in synaptic facilitation and potentiation and indicate that synaptic plasticity is altered in memory mutants.
Mutations in dnc affect sensory fatigue due to anteronotopleural bristle deflection, not sensory adaptation.
Mutant analysis provides evidence for the participation of a G0-like protein in learning and memory.
Mutations in dnc significantly reduce the females song memory after prestimulation with courtship hums. This suggests a simple sensitization process may be involved with the female pulse song memory (Kyriacou and Hall, Nature 308: 62).
Df(1)N-71h/Df(1)dm75e19 females survive, even though they are completely deleted for some five bands, including 3D4; such females are defective in learning and are sterile. dncM11-induced sterility partly suppressed by rut (Livingstone, Sziber and Quinn, 1984) and this phenotype of the double mutant used to select two new purported rut alleles, one of which (rut2) also suppresses learning defects associated with dncM14 (Feany, 1990).
Gene encodes a cAMP-specific phosphodiesterase. Mutants blocked or impaired in learning, with respect to several of the conditioning tests used on groups of flies or larvae or on individual adults, e.g., those involving odors and electric shocks or sugars (Aceves-Pina and Quinn, 1979; Tempel, Bonini, Dawson and Quinn, 1983; see also Aceves-Pina, Booker, Duerr, Livingstone, Quinn, Smith, Sziber, Tempel, and Tully, 1983), visual stimuli (Folkers, 1982), or various elements of courtship (with respect to tests on mutant males or females, summarized by Hall, 1984); also, dncM14 males have reduced reproductive fitness after exposure to and courtship of immature females, i.e. when mutant males are put, post-training, with mixed female/young male populations (Gailey et al., 1985). dnc females display an increased frequency of mating; it is suggested that this could account for their 50% normal longevity (Bellen and Kiger, 1987). dnc males are not conditioned to avoid virgin females by sequestration with such females in the presence of quinine; wild type males are (Ackerman and Siegel, 1986). dnc mutants apparently learn normally, or nearly so, in certain experiments but have abnormally short memory (e.g., Dudai, 1979; Mariath, 1985); more specifically, modifications of original shock-odor testing system reveal that dnc is defective in short term memory, with long-term memory similar to wild type (Tully and Quinn, 1985); dnc/+ females also memory deficient (Dudai, 1983). Whereas dnc adults seem normal in several general behaviors (Dudai, Jan, Byers, Quinn and Benzer, 1976), the mutant displays aberrant 'centrophobic' behavior [i.e., transient avoidance of the center of an arena displayed by normal adults (Gotz and Biesinger, 1985). Mosaic studies suggest that the focus of dnc/+ function is the brain, even though some learning responses demonstrated by headless flies (Aceves-Pina, Booker, Duerr, Livingstone, Quinn, Smith, Sziber, Tempel, and Tully, 1983). Sensory fatigue associated with an adult mechanosensory neuron, as measured by bristle stimulation, occurs more rapidly than normal in dnc (allele not specified) (Corfas and Dudai, 1990). There is an increased number of mushroom-body axonal fibers in young adults expressing dnc1 or dncM11, which, unlike wild type, decreases over the next few days (Balling, Technau, and Heisenberg, 1987). Mutations or deletions of the locus reduce or eliminate one form of cyclic AMP phosphodiesterase activity; caffeine, an inhibitor of this enzyme, decreases visual learning performance of normal adults and of dnc1 as well, suggesting that the biochemical effects of the drug and the mutation are not identical (Folkers and Spatz, 1984). The effects of dnc mutations on heat stability or Km of this activity indicate that the locus codes for this enzyme (Kauvar, 1982; Davis and Kauvar, 1983); dnc variants also lead to increased levels of cyclic AMP (summarized by Davis and Kauvar, 1983), more specifically, such that most of the excess is in free (vs. bound) nucleotide; both fractions exist in whole-fly homogenates (Friedrich, Solti, Gyurkovicz, 1984). dncM11 affects the level of phosphorylation of the regulatory subunit of the cyclic-AMP-dependent kinase (Devay, Pinter, Yalcin and Friedrich, 1986). Levels of regulatory subunit of cAMP-dependent protein kinase tend to be higher than normal in dnc1 and dnc2 (Muller and Spatz, 1989). dncM11 flies exhibit increased levels of expression of copia (Yun and Davis, 1989). dnc alleles cause varying degrees of female sterility; oocytes of females homozygous for amorphic alleles rarely reach maturity, and for the most part are not oviposited; 90% of the few that are oviposited are fragile, lacking a chorion. That this phenotype is somatic in origin is demonstrated by the observation that homozygous germ-line clones produce morphologically normal eggs; some of these eggs undergo a few abortive nuclear divisions, but they never reach an identifiable stage of oogenesis. The maternal-effect lethality partially suppressible by rut, which reduces adenylate cyclase activity. The earliest defect seen in the embryos produced by dnc rut females occurs soon after fertilization and affects DNA replication and mitosis, prevents nuclear migration and leads to large polyploid nuclei; a later defect prevents cleavage nuclei from migrating into, or dividing in, the posterior region of the egg, affecting the developmental behavior or fate of blastoderm cells. The few surviving offspring of double-mutant females show frequent developmental abnormalities of the second and third thoracic and the first five abdominal segments; these include deficiencies, duplications and transformation of structures; some 15% of the daughters of such females lack one or both ovaries (Livingstone, Sziber and Quinn, 1984; Bellen, Gregory, Olsson, and Kiger, 1987; Bellen and Kiger, 1988).
The term "dunce" refers to John Duns Scotus, 13th century opponent to the revival of classical learning.