Role of Nanomaterials on Retromer Complex and its Consequences on the Development and Maintenance of Sensory Organ of Drosophila

Abstract

The current era utilizes nanomaterials in several branches of science including many dayto- day applications. With the wide application, toxic reports are also coming from several studies. There are many open questions associated with nanoparticle trafficking. It includes (1) does the oral intake of nanoparticle (NP) causes developmental and behavioral toxicity? (2) Does the toxicity is a function of defective molecular machinery? (3) Does the toxicity depend on the shape and size of the NP? (4) Does the in vivo toxicity is linked with the malformed gene which occurs during the transportation? These questions are answered in this thesis. The first objective estimated the oral toxicity of different concentrations (10 mg.L-1, 20 mg.L-1, 40 mg.L-1, and 80 mg.L-1) of rod-shaped hydroxyapatite NP (HApNP) on the first instar larva of Drosophila. HApNP affects the development and behavior associated with the eye and mechanosensory organ throughout the development. The eye and mechanosensory organ defects start at the larval stage and persist till adult. All the phenotypic defects were further correlated due to the downregulation of the retromer complex involved in the transportation. The second objective checks the oral toxicity of spherical-shaped silica nanoparticles (SiO2NP) on Drosophila. The 1st instar larvae were fed with different concentrations (5 mg.L-1, 10 mg.L-1, 20 mg.L-1, and 40 mg.L-1) of SiO2NP. The defects were seen from larvae to adults. The defects were seen in the redox pathway, eye, and mechanosensory organs. SiO2NP binds strongly to the actin and thus forms a pore in the membrane. Like HApNP, SiO2NP also causes downregulation of the retromer complex. Since both the nanoparticle affects the retromer during transportation it is worthy to check how the retromer mutant affects the development and behavior associated with the eye and mechanosensory organ. The third objective aims to generate the clone of one of the key components of the retromer complex i.e. Vps35. The photoreceptor and mechanoreceptor clones were generated and the structure, as well as behavior associated with the mechanosensory organs, was investigated. The defects were seen in the antennae, haltere, and ocelli of the clones. The size of the third segment of the antennae was smaller in clones in comparison to the control. Extra bristles were seen in clone heads than that of control. In association with structural deformities, the antennal behavior was also getting interrupted in clones like aggressive, geotaxis, courtship behavior, etc. The simple eye ocelli were also being affected in clones with some overgrowth unlike the control and intra ocellar bristles were also being altered in clones. The circadian rhythm was also being affected in clones which in turn disturbed the light sensitivity in clones suggesting the role of Vps35 not in the development but also in the other cellular pathways associated with the social life of the fly. The number of campaniform sensilla is reduced in the haltere structure of clones. Down regulation of the Iav, Pyx, Nan, NompC suggested a defect in the transportation of antennal signaling molecules in Vps35 mutants.