Some retinal degeneration is observed in 7-day old flies expressing Hsap\MAPT^Scer\UAS.cAa under the control of Scer\GAL4^GMR.PU.

Expression of Hsap\MAPT^Scer\UAS.cAa under the control of Scer\GAL4^D42 exhibit locomotion defects.

Larvae expressing Hsap\MAPT^Scer\UAS.cAa in the motor neurons, under the control of Scer\GAL4^D42, manifest a number of distinct phenotypes including crawling defects in larvae. This defective, non-continuous crawling behaviour is significantly improved following treatment with a microtubule-stabilising drug, NAPVSIPQ (NAP), leading to smoother, more directed movement over a greater distance, as in controls. Treatment with 2.5υg ml[-1] significantly improves body wall contractions and velocity, compared with untreated Hsap\MAPT^Scer\UAS.cAa flies. Meander is also improved, but not significantly.

Peripheral nerves in larvae expressing Hsap\MAPT^Scer\UAS.cAa in the motor neurons, under the control of Scer\GAL4^D42, exhibit disorganised and mis-aligned microtubules. Treatment with NAP re-stabilises the disrupted and disorganised microtubules.

Axonal transport is disrupted in Scer\GAL4^D42>Hsap\MAPT^Scer\UAS.cAa larvae. Treatment with NAP rescues axonal transport.

Expression of Hsap\MAPT^Scer\UAS.cAa in larvae neuromuscular junctions, under the control of Scer\GAL4^D42, results in profound morphological aberrations in the NMJ, including thinning of inter-bouton axon segments and appearance of 'mini' satellite boutons.

Flies expressing Hsap\MAPT^Scer\UAS.cAa under the control of Scer\GAL4^D42 show a great turning rate per distance moved than controls. This increase in turning rate is not rescued by feeding the flies the hsp70 inhibitor compound 17-AAG, and is worsened by radiocol, celastrol and simvastatin.

The axons of larvae expressing Hsap\MAPT^Scer\UAS.cAa under the control of Scer\GAL4^elav.PU have fewer correctly-aligned transverse microtubule profiles than control larvae when analysed ultrastructurally and there is evidence of disorganised microtubules in the same axon profiles.

Expression of highly phosphorylated Hsap\MAPT^Scer\UAS.cAa in neurons is associated with a loss of detectable microtubule profiles in axons.

Expression of Hsap\MAPT^Scer\UAS.cAa under the control of Scer\GAL4^elav.PU does not affect the mushroom bodies appreciably.

Expression of Hsap\MAPT^Scer\UAS.cAa under the control of Scer\GAL4^elav.PU does not result in any obvious neuronal toxicity or associative learning defects.

All Scer\GAL4^D42>Hsap\MAPT^Scer\UAS.cAa larvae exhibit a clear locomotor dysfunction. The most severely affected larvae show complete paralysis of the posterior end and a tail flipping phenotype characterised by curling of the posterior.

Many of the Scer\GAL4^D42>Hsap\MAPT^Scer\UAS.cAa-expressing larvae pupate and eclose to become viable adults.

For the first 15 days post-eclosion there is no significant difference between Scer\GAL4^D42>Hsap\MAPT^Scer\UAS.cAa-expressing and control flies in climbing ability. After 15 days, however, the performance of flies expressing Hsap\MAPT^Scer\UAS.cAa under the control of Scer\GAL4^D42 show a significantly greater deterioration in climbing assays compared with age-matched controls.

In the presence of Scer\GAL4^D42>Hsap\MAPT^Scer\UAS.cAa-expression, vesicle transport in motor axons including the main intersegmental regions, the second-order nerve branches and at the neuromuscular junction (NMJ). Instead of the even distribution that characterise the axons of the control larvae, in Scer\GAL4^D42>Hsap\MAPT^Scer\UAS.cAa-expressing axons vesicles accumulate into large axonal swellings that appear as "vesicular aggregations" of variable sizes along the length of the axon.

Over-expression of Hsap\MAPT^Scer\UAS.cAa under the control of Scer\GAL4^D42 disrupts axonal transport without affecting the speed of individual vesicles.

The neuronal cell body counts for motor neurons in Scer\GAL4^D42>Hsap\MAPT^Scer\UAS.cAa-expressing larvae are identical to those seen in control larvae.

LiCl or AR-A014418 treatment suppresses the Scer\GAL4^D42>Hsap\MAPT^Scer\UAS.cAa-induced locomotor and axonal transport phenotypes.

Expression of Hsap\MAPT^Scer\UAS.cAa under the control of Scer\GAL4^smid-C161 results in defects in the axon projections in the prothoracic neuromere in adults (analysed 24 hours after eclosion at 25^oC). Loss of the medial projection, abnormal axon bundling and beading is seen. Randomly projecting, fine branches that do not fit with the normal morphology of the neurons are also seen. Flies maintained at 25^oC for 7 days show the same defects of axon loss and axon bundling as seen in 24 hour old adults, but there is a more severe level of axon beading in the 7 day old flies (both the number and size of beads is increased).

Hsap\MAPT^UAS.cAa, Scer\GAL4^GMR.PU has abnormal neuroanatomy phenotype, enhanceable by tau^GD8682, Scer\GAL4^GMR.PU

Hsap\MAPT^UAS.cAa, Scer\GAL4^Toll-6-D42 has abnormal locomotor behavior | third instar larval stage phenotype, enhanceable by sgg^S9A.UAS, Scer\GAL4^Toll-6-D42