Flies expressing Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP} under the control of Scer\GAL4^GMR.PF begin to show obvious loss of ommatidia at eclosion with different level of severity. Although there are significant variations in the eye defects among individual flies of the same age and the same genetic background, Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP}-expressing flies show progressive degeneration with aging. The organisation of ommatidia is completely lost in Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP}-expressing flies, with large vacuoles frequently detected, although their cone cells remain largely normal. The normal rhabdomere arrangement is disrupted in Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP}-expressing flies as early as day 1 after eclosion, with very few rhabdomeres detected. By day 30 after eclosion, the rhabdomere structure is completely lost in Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP}-expressing flies with morphological features of neurodegeneration including degenerating mitochondria, multi-lamellar bodies, multi-vesicular bodies, and autophagic vacuoles.

Axon bundles are much thinner or completely lost as early as day 1 after eclosion in mushroom bodies expressing Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP} under the control of Scer\GAL4^ey-OK107. There are remarkable variations in axonal defects among different flies with the same genetic background, involving different mushroom body (MB) lobes. The remaining axons in each individual brain are often derived from one subtype of MB neurons. Neurons in the Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP}-expressing MBs degenerate in an age-dependent manner. Compared with the normal lobe structures observed in controls, MBs expressing Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP} show only residual axon bundles. In addition, these Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP}-expressing MB neurons in aged flies show obvious signs of axon degeneration, including a loss of axon integrity and increased abnormal axonal varicosities.

Calyx structures of MBs expressing Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP} under the control of Scer\GAL4^ey-OK107 show a dramatic loss of neurons with significant variations in severity. Three to six apoptotic cells are frequently found in each calyx of Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP}-expressing MBs. No apoptotic cells are detected in age-matched controls.

Expression of Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP} in motor neurons (MNs) under the control of Scer\GAL4^VGlut-OK371 engenders aggregate formation in the expressing cell bodies and axons, together with axon swelling. MNs of late third instar larvae expressing Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP} under the control of Scer\GAL4^VGlut-OK371 are not organised in their normal clusters as in controls, showing cell loss. Such MN loss is more severe in the posterior abdominal segments as compared with the anterior ones. MNs expressing Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP} show a significant decrease in the number of both big and small boutons, and of the axon branches as compared with controls.

The locomotive ability of animals expressing Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP} under the control of Scer\GAL4^VGlut-OK371 is significantly impaired at both larval and adult stages.

Most flies expressing Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP} under the control of Scer\GAL4^VGlut-OK371 die at or before eclosion.

As compared with controls, flies expressing Hsap\TARDBP^{Scer\UAS.T:Ivir\haemagglutinin,T:Disc\RFP} in a small subset of motor neurons at the adult stage under the control of Scer\GAL4^eve.RN2 show a reduction in their motility, becoming progressively worse with aging and with the difference significant from day 10 after eclosion.

Hsap\TARDBP^{UAS.Tag:HA,RFP(Unk)}, Scer\GAL4^VGlut1-OK371 has abnormal locomotor behavior | late third instar larval stage phenotype, suppressible by TBPH^GD6943, Scer\GAL4^VGlut1-OK371