Browsing by Author "Vonhoff, Fernando J."
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Item Candidate Autism Gene NRX1 Leads to Ectopic Synapses in Nociceptive Neurons in Drosophila Larvae(IBRO Neuroscience Report, 2023-10) Gualtieri, Claudia; Vonhoff, Fernando J.Synaptic pruning is a neuroplastic process leading to the withdrawal of ectopic synapses formed during the initial phases of neuronal development. Extensive research has shown evidence of synaptic pruning occurring in both the central nervous system (CNS) and peripheral nervous system (PNS). However, the molecular mechanisms underlying synaptic pruning remain incompletely understood. The process of synapse pruning is crucial during development in multiple organisms as it has also been linked to the onset of neurodevelopmental disorders like autism. We determined the anatomical effects of candidate autism genes in vivo using the Drosophila model. Starting from the hypothesis that candidate autism genes would lead to the presence of ectopic synapses that branch off stereotypic connectivity patterns, we assessed the stereotypic synaptic innervations of cIV nociceptive sensory neurons development. The candidate autism genes of the transsynaptic adhesion proteins neurexin-1 and neuroligin-3 were downregulated using RNAi constructs. Anatomical defects were assessed by counting the number of ectopic neurites. Data shows increased number of ectopic neurites in the stereotypic ladder structure formed in the CNS by the axonal projection of nociceptive neurons when the candidate autism gene neurexin-1 is downregulated. Additionally, we are in the process of assessing the synaptic connectivity between cIV sensory neurons and the postsynaptic basin interneurons during embryonic and larval development using the GFP Reconstitution Across Synaptic Partners (GRASP) technique. This data will reveal the synaptic partnership between nociceptors and basin interneurons -1 and -4 at different stages of Drosophila development. Also, it will provide the groundwork for determining the potential role of synaptic pruning on the synaptic connectivity of nociceptors to basins, offering the setting for future pruning disruption investigations. Our findings will offer the basis for investigating the processes leading to the failure in the elimination of ectopic synapses providing insights into the molecular mechanisms regulating synaptic refinement.