Homozygous mutants display ~97% lethality throughout larval and pupal development.
~12% of disco1/disco1656 pupae and adult escapers show antenna phenotypes, characterized by the disruption and deletion of the arista and the partial truncation of antennal segment 3.
~5% of disco1/disco1656 pupae show leg phenotypes, mostly characterized by the shrinkage of the femur and tibia, and the deletion of the distal tarsal segments and claw.
In mosaic adults in which one central brain hemisphere is disco1 homozygous, while the other central brain hemisphere and both optic lobes are wild-type (generated by the ring-X gynandromorph mosaic technique), Pdf-expressing lateral neurons (LNs) are absent from the mutant hemisphere. Pdf-expressing LNs from the wild-type hemisphere project, as normal, from the wild-type hemisphere via the posterior optic tract into the mutant, contralateral hemisphere, where they arborize in the (wild-type, contralateral) medulla. If the entire contralateral hemisphere, including the optic lobe is disco1 homozygous, the mutant optic lobe degenerates. In this case, the wild-type Pdf-expressing LNs project normally from the wild-type hemisphere through the posterior optic tract but then arborize aberrantly in the mutant hemisphere.
Mutant larvae do not have defects in the establishment or maintenance of dendritic tiling in class IV dendrite arborisation (da) neurons.
In disco1 mutant larvae, the optic stalk is absent and photoreceptor axons remain within the eye disc, where they extend and form basal tangles.
Most ventral lateral neurons are missing, however, some ventral lateral neurons are still present in the majority of disco1 mutant larval and adult brains. The lack of the dorsally projecting Scer\GAL41118-expressing neurons is evident in some of the disco1 mutant flies.
Approximately 67% of disco1 mutant flies do not show rhythmic behaviour in locomotor activity. The remaining flies that show rhythmic behaviour display a mean period 2.5-3.7h shorter than the corresponding controls. The majority of these mutants show weak short period rhythms. Approximately 2% of the mutants display a robust circadian rhythm indistinguishable from wild-type. In light-dark conditions, the evening activity peak of disco1 flies is advanced compared to controls, consistent with a fast-running clock. The distribution of the average activity over a 24-h window shifts from nonrandom during the first 2 days in constant darkness to random during the next two days, indicating that the disco1 flies transiently keep a synchronized rhythmic behaviour.
Homozygous embryos develop into normal larvae with an occasional, slight reduction in the mouth hook base.
Loss of disco activity in the disco1 allele has no apparent effect on the cellular identity or differentiation of the majority of the cells in the optic lobe primordium.
Flies are behaviourally arrhythmic when locomotor activity is measured under constant darkness conditions.
Hemizygous male larvae and pupae show defects in the central projections of proprioceptive sensory neurons. The basic segmentally repeated pattern of the central projections is still seen in hemizygous larvae. Central projection defects seen in larvae include axon weaving - axons are not rigidly aligned and meander towards the midline, defects in axon bundling resulting in a poorly defined array, excessive growth of axons close to the midline where they normally terminate, resulting in axon tangles, and aberrant projections of some axons. Disruption of projections of sensory axons from the leg are seen in pupae; meandering growth, less tight axon bundling and loss of axon fasciculation are seen. The pupal central nervous system (CNS) shows aberrant growth of axons and the formation of axon tangles. Ectopic innervation of the CNS is seen in the thoracic neuromeres. Similar defects are seen in projections of axons from sensory neurons on the wing and haltere. Axons projecting from the multiscolophorous organ in the abdomen are not as tightly bundled as normal and show excessive branching. Approximately one-third of homozygotes die as larvae, approximately one-third die as pupae and the remainder form pharate adults. Homozygous female and hemizygous male larvae have significantly lower motility than their control siblings.
Ventral lateral neurons (LNVs) are occasionally present an provoke robust circadian rhythmicity in mutants. Of 357 flies 4 exhibit robust circadian rhythmicity. All four retained LNVs together with terminals in the superior protocerebrum. Residual or bi-circadian rhythmicity is found in 20% of all flies, the remaining are completely arrhythmic.
Mutant larvae exhibit absence of a cluster of small PDFMe neurons and supernumerary PDFCa neurons. Cluster of PDH-immunoreactive neurons lying in the ventral ganglion is indistinguishable from wild type. In pupae large PDFMe neurons are not found and the PDFTri neurons develop normally. In adults the PDH immunoreactivity in the somata of PDFTri neurons is usually dispersed within 24 hours after eclosion (as in wild type) but immunoreactivity in the aborizations of these neurons persists somewhat longer.
Larval optic nerve cannot establish proper connections with its target cells during embryonic development, phenotype is due to the absence of the optic stalk so that the larval optic nerve cannot not enter the larval brain (unconnected phenotype). The larval optic nerve can be found in abnormal locations (connected phenotype).
Imaginal photoreceptor axons fail to reach their target cells during the third larval instar: disrupt optic lobe development. Adults exhibit a rudiment of the optic lobe. In aged unconnected eyes R1--R7 cells degenerate, demonstrated by specific staining of the R cells using Rh4 and ninaE Ecol\lacZ reporter gene fusions.
Reduction in fibre number in the anterior optic tracts.
Unstable connections between larval optic nerves and aberrant development of the optic lobes that degenerate in adult fly.
Viable. Adult eye and optic lobes have defects. The unconnected phenotype exhibits photoreceptors that degenerate with age, disorganized muscle tissue fills the space normally occupied by optic ganglia: flies are blind. The connected phenotype exhibits photoreceptor axons that innervate the optic ganglia, structure is disorganized and distinguishable from wild type. Extensive degeneration of photoreceptor cells becomes apparent in the form of dark spots on the compound eye.
Compound eyes are disconnected from optic ganglia in most mutant individuals, but approximately 5-10% have superficially normal eye-brain connections. Photoreceptor cells initially present but degenerate progressively with age; axons of photoreceptor cells which are still present form plexus beneath the eye. Focus of gene function fate maps to a point well anterior to the focus of either the eye or optic lobe (Fischbach). Adult defect arises as consequence of a defect in the larval visual nerve (Bolwig's nerve) which fails to connect with its target cells in the central nervous system; subsequently, owing to loss of the pioneer function of Bolwig's nerve, retinular axons fail to innervate their target cells in the developing optic lobes leading to massive degeneration of the optic ganglia during the early pupal stages (Steller, Fischbach and Rubin, 1987). Slight disarray of embryonic peripheral nervous system detectable; occasional errant neurons seen. Developing CNS appears normal, but adult brain is abnormal in that certain lateral neurons, which normally express per are either absent or do not express per (Zerr, Hall, Rosbasch and Sibicki, 1980). Larval reacts normally to all stimuli except light. All alleles display significantly reduced viability; death occurs in late pupal stages as pharate adults. In tests of circadian rhythms, eclosion and adult locomotor activity are essentially arrhythmic (Dushaym Rosbasch and Hall, 1989). Cyclical expression of per protein, which normally occurs in eyes and brain, is fairly robust in disco, whether eyes connected to the brain or not (Zerr, Hall, Rosbasch and Sibicki, 1980); hence this eye rhythm may be autonomous, i.e., given absence of CNS neuronal staining in mutant adults. reduced viability.