Exploracion de la interaccion neuroligina-fmrp durante el proceso de poda axonal posnatal dependiente de actividad en cepas silvestres y mutadas de drosophila melanogaster.

Early synaptogenesis proceeds as a largely activity-independent process while the later refinement of synapses involves activity-dependent (a-D) mechanisms especially during the early critical periods of postnatal development, when synaptic arrays experience both new additions and active pruning. Several studies have pointed out that these a-D developmental processes, which play a pivotal role in the refining of the brain circuitry, are specifically impaired in neurological disorders like fragile X syndrome (FXS) and autism spectrum disorders (aSDs). FXS is the most common inherited cause linked to aSDs: approximately 15%-33% of FXS patients also have autism. The leading cause of FXS is the transcriptional silencing of the fragile X mental retardation protein (FMRP). Evidence has shown that during the early-use critical periods of postnatal development FMRP is strongly upregulated. FXS patients and FMRP deficient mutant mice and Drosophila all have overgrown dendritic arbors with immature dendritic spines suggesting that the processes of synaptic pruning and synapse maturation are affected in both the human disease and in FXS animal models. Neuroligins (Nlgs) are a family of synaptic adhesion transmembrane proteins that lead the formation of presynaptic and postsynaptic structures. after mutations in the human Nlgs were discovered in aSD patients, increasing evidence has indicated that Nlgs expression is critical for synapse maturation and function and a recent study demonstrates the involvement of Nlgs in central symptoms of FXS. To explore an Nlgs-FMRP interaction involved in the molecular mechanisms stimulated during a-D synaptic pruning, we propose to initiate a collaborative research project to study these two proteins in Drosophila wildtype and null dfmr1 mutant strains during normal sensory exposition and during a sensory experience deprivation rearing protocol. Our aim in this study is to evaluate Nlgs expression during early postnatal developmental phases in Drosophila wildtype and null dmfr1 mutant strains.