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,
Science 206: 93-96; Tempel, Bonini, Dawson, and Quinn, 1983,
Proc. Nat. Acad. Sci. USA 80: 1482-86; see also Aceves-Pina,
Booker, Duerr, Livingstone, Quinn, Smith, Sziber, Tempel, and
Tully, 1983, Cold Spring Harbor Symp. Quant. Biol. 48: 831-40), visual stimuli (Folkers, 1982, J. Insect Physiol.
28: 535-39), or various elements of courtship (with respect
to tests on mutant males or females, summarized by Hall, 1984,
Dev. Genet. 4: 355-78); 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, Siegel, and
Hall, 1985, Genetics 111: 795-804). dnc females display an
increased frequency of mating; it is suggested that this could
account for their 50% normal longevity (Bellen and Kiger,
1987, Genetics 115: 153-60). 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, J. Neurogenet. 3: 111-23). dnc mutants
apparently learn normally, or nearly so, in certain experiments but have abnormally short memory (e.g., Dudai, 1979, J.
Comp. Physiol. 130: 271-75; Mariath, 1985, J. Insect Physiol.
31: 779-87); more specifically, modificatons 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, J. Comp. Physiol. 157: 263-77); dnc/+
females also memory deficient (Dudai, 1983, Proc. Nat. Acad.
Sci. USA 80: 5445-48). Whereas dnc adults seem normal in
several general behaviors (Dudai et al., 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, J. Comp. Physiol. 156: 319-27,
329-37)]. Mosaic studies suggest that the focus of dnc/+
function is the brain, even though some learning responses
demonstrated by headless flies (Aceves-Pina, et al.). 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, J.
Neurosci. 10: 491-99). 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, J. Neurogenet.
4: 65-73). Mutations or deletions of the locus reduce or
eliminate one form of cyclic AMP phosphodiesterase (EC
188.8.131.52) 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, J. Insect Physiol. 30: 957-65). The effects of dnc
mutations on heat stability or Km of this activity indicate
that the locus codes for this enzyme (Kauvar, 1982, J. Neurosci. 2: 1347-58; Davis and Kauvar); 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, J.
Cell. Biochem. 26: 197-203). dncM11 affects the level of
phosphorylation of the regulatory subunit of the cyclic-AMP-dependent kinase (Devay, Pinter, Yalcin, and Friedrich, 1986,
Neurosci. 18: 193-203). Levels of regulatory subunit of
cAMP-dependent protein kinase tend to be higher than normal in
dnc1 and dnc2 (Muller and Spatz, 1989, J. Neurogenet. 6: 95-114). dncM11 flies exhibit increased levels of expression of
copia (Yun and Davis, 1989, Nucleic Acids Res. 17: 8313-26).
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 poserior 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, Cell 37: 205-15; Bellen, Gregory, Olsson,
and Kiger, 1987, Dev. Biol. 121: 432-44; Bellen and Kiger,
1988, Roux's Arch. Dev. Biol. 197: 258-68).