The neuroepithelia of both inner and outer optic anlagen are massively expanded in mutant early third instar larvae. This initially leads to a delay in optic lobe neuroblast formation, but optic lobe neuroblasts do form later and their number is significantly increased compared to wild type. Neuroblast formation is seen in the centre of the optic lobe epithelium, in contrast to wild type.
Homozygous larval brain tissue develops into tumours after allograft into adult host flies (taking over the entire abdomen of the host) in 70% of cases.
When pieces of brain from l(3)mbtts1 9-12-day-old larvae, which show tissue overgrowth, are transplanted into the abdomens of adult hosts, tumors of the abdomen develop.
Homozygous larvae carrying l(3)mbt+t6.8 show normal development of the brain, pupate like wild-type and viable fertile adults hatch.
Homozygotes develop into fertile adults at the permissive temperature (22oC), but die shortly after pseudo-puparium formation at the restrictive temperature (29oC). The third larval instar stage is greatly extended at 29oC, and can last up to three weeks. The brain hemispheres are up to five times larger in older homozygous larvae raised at the restrictive temperature than in mature wild-type larvae. The mutant brain hemispheres show a highly distorted internal morphology, and are composed of numerous large neuroblasts and ganglion mother cells. The central neuropile is destroyed by the invasively growing neoplastic cells and in advanced tumours the cells may also invade the ventral ganglion. Mutant brain tissue injected into the abdomens of wild-type females develops into immense lethal tumours, indicating that the mutant cells are malignant. Mutant larvae raised at 29oC begin to show abnormalities in the spatial separation of the outer and inner optic anlagen of the brain by 40 hours of development. As the larvae age, the abnormalities in the presumptive adult optic centres become more pronounced. Mutant imaginal discs show growth abnormalities at 29oC; the growth rate of the discs is slower than wild-type during early development, so that at 72 hours of development the mutant wing imaginal disc is often five times smaller than the wild-type. However, mutant and wild-type wing imaginal discs are a similar size at the time at which wild-type pupariation occurs. The wing disc epithelium becomes progressively hyperplastic and abnormally folded during the extended larval instar period. Wing imaginal disc tissue transplanted into wild-type larvae can differentiate into normal adult structures. Wing imaginal disc tissue transplanted into the abdomens of wild-type females retains the epithelial overgrowth phenotype, but does not kill the host, indicating that mutant imaginal discs are non-tumorous. Temperature-shift experiments indicate that the temperature-sensitive period for brain tumour suppression and normal imaginal disc development encompasses the first six hours of embryonic development. l(3)mbt function is also required throughout the remainder of development for the proper differentiation of the brain and imaginal discs.
Homozygous larvae develop malignant neuroblastomas in the presumptive adult optic centres of the brain at 29oC. These tumours consist of neuroblasts and ganglion mother cells which are unable to differentiate into optic neurons and show a characteristic pattern of malignant growth. All portions of the brain become invaded by the tumorous cells, and ultimately the larvae become bloated. These larvae fail to pupariate, or form a puparium with a delay of 2 to 7 days, and die shortly thereafter. Implantation of l(3)mbtts1 brain pieces into wild-type flies leads to malignant tumours, which invade the fat body, gut, thoracic muscles and the head, causing death of the host in 10 to 14 days. Imaginal discs are slightly enlarged at the restrictive temperature, but have an apparently normal folded pattern. These imaginal discs differentiate into cuticular structures when transplanted into wild-type larvae which are about to pupariate.