The Role Of ASD Susceptibility Gene Neuroligin3 In Transcriptional Regulation

Abnormal development of the nervous system can lead to neurological disorders,such as autism.On the other hand,synaptic adhesion molecules play a very important role in the differentiation and development of neurons.Neuroligin3 is not only a transmembrane protein in the presynaptic and posterior membrane,but also a susceptible gene for autism.Recent studies have found that Neuroligin3 plays an important role in synaptic maturation and NMJ differentiation and development,but its specific mechanism is not clear.In this study,Drosophila melanogaster was used as a model organism to study the mechanism of neuroligin3 in the development of neurotransmitters by high-throughput sequencing and biochemical methods.Drosophila Neuroligin3 is highly homologous to vertebrate Neuroligin and contains 1158 amino acids.As a transmembrane protein,the extracellular domain has an acetylcholine-like domain and PDZ binding domain.Studies have shown that Neuroligin3 intracellular segmentation localized in the nucleus.However,the physiological significance of this co-localization phenomenon is not clear.Previous studies suggest that autism patients with cerebral cortex have a large number of differential expression genes.We speculate that Neuroligin3 involves in the development of the nervous system by influencing the expression of genes.In order to explore our hypothesis,first we detected the intracellular segment of Neuroligin3 in Drosophila S2 cells.Cell immunofluorescence staining showed that intracellular segment of Neuroligin3 localized in the nucleus,and this segment could be detected in the nucleoprotein,indicating that Neuroligin3 was possibly involved in the regulation of gene expression.Second,the heads of wild-type adults(W1118)and neuroligin3 mutants were sampled and analyzed by RNA-seq,The results showed that the mutation of neuroligin3 resulted in differential expression of genes.The GO analysis indicated that Neuroligin3 regulated the expression of the nervous system gene.It was found that the down-regulated genes were involved in development.In summary,this study complements the prior work of our laboratory and the nuclear entrance of intracellular segment of Neuroligin3.Transcriptome sequencing confirms that the expression of the nervous system genes were regulated in neuroligin3 mutants,and these genes will seriously affect differentiation and development of the nervous system.This study further provides a new insight into the mechanism of Neuroligin3 in the developmental differentiation of the nervous system,which further reflects the important role of synaptic adhesion molecules in the developmental differentiation and nervous system disease.