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The 1p32.3 chromosomal region harbors several genes critical for development; however, their validation and characterization remain inadequate. One such gene is the single-stranded DNA-binding protein 3 (\n                    <jats:italic>SSBP3<\/jats:italic>\n                    ) and its\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    ortholog is called sequence-specific single-stranded DNA-binding protein (\n                    <jats:italic>Ssdp<\/jats:italic>\n                    ). Here, we investigated consequences of\n                    <jats:italic>Ssdp<\/jats:italic>\n                    manipulations on neurodevelopment, gene expression, physiological function, and autism-associated behaviors using\n                    <jats:italic>Drosophila<\/jats:italic>\n                    models. We found that SSBP3 and Ssdp are expressed in excitatory neurons in the brain.\n                    <jats:italic>Ssdp<\/jats:italic>\n                    overexpression caused morphological alterations in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    wing, mechanosensory bristles, and head.\n                    <jats:italic>Ssdp<\/jats:italic>\n                    manipulations also affected the neuropil brain volume and glial cell number in larvae and adult flies. Moreover,\n                    <jats:italic>Ssdp<\/jats:italic>\n                    overexpression led to differential changes in synaptic density in specific brain regions. We observed decreased levels of armadillo in the heads of\n                    <jats:italic>Ssdp<\/jats:italic>\n                    overexpressing flies, as well as a decrease in armadillo and wingless expression in the larval wing discs, implicating the involvement of the canonical Wnt signaling pathway in Ssdp functionality. RNA sequencing revealed perturbation of oxidative stress-related pathways in heads of\n                    <jats:italic>Ssdp<\/jats:italic>\n                    overexpressing flies. Furthermore,\n                    <jats:italic>Ssdp<\/jats:italic>\n                    overexpressing brains showed enhanced reactive oxygen species (ROS), altered neuronal mitochondrial morphology, and up-regulated fission and fusion genes. Flies with elevated levels of\n                    <jats:italic>Ssdp<\/jats:italic>\n                    exhibited heightened anxiety-like behavior, altered decisiveness, defective sensory perception and habituation, abnormal social interaction, and feeding defects, which were phenocopied in the pan-neuronal\n                    <jats:italic>Ssdp<\/jats:italic>\n                    knockdown flies, suggesting that\n                    <jats:italic>Ssdp<\/jats:italic>\n                    is dosage sensitive. Partial rescue of behavioral defects was observed upon normalization of\n                    <jats:italic>Ssdp<\/jats:italic>\n                    levels. Notably,\n                    <jats:italic>Ssdp<\/jats:italic>\n                    knockdown exclusively in adult flies did not produce behavioral and functional defects. Finally, we show that optogenetic manipulation of Ssdp-expressing neurons altered autism-associated behaviors. Collectively, our findings provide evidence that\n                    <jats:italic>Ssdp<\/jats:italic>\n                    , a dosage-sensitive gene in the 1p32.3 chromosomal region, is associated with various anatomical, physiological, and behavioral defects, which may be relevant to neurodevelopmental disorders like autism. Our study proposes\n                    <jats:italic>SSBP3<\/jats:italic>\n                    as a critical gene in the 1p32.3 microdeletion\/duplication genomic region and sheds light on the functional role of\n                    <jats:italic>Ssdp<\/jats:italic>\n                    in neurodevelopmental processes in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3002210","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T13:26:23Z","timestamp":1690205183000},"page":"e3002210","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["The ortholog of human ssDNA-binding protein SSBP3 influences neurodevelopment and autism-like behaviors in Drosophila melanogaster"],"prefix":"10.1371","volume":"21","author":[{"given":"Safa","family":"Salim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadam","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha","family":"Banu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swetha B. 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