Study On Molecular And Cellular Mechanisms Of MADD-4B Regulating Synaptic Remodeling Of DD Motor Neurons

The brain function of normal neural network depends on neural circuits correctly,and abnormal synaptic connections can lead to abnormal neural circuits,causing nervous system disease and mental disease.Synapse is a specialized structure for the exchange of information between neurons and between neurons and other cells.Synaptic mainly include chemical synapses and electrical synapses.For a long time,especially the development and remodeling of chemical synapses is the core of scientific research in neuroscience.Caenorhabditis elegans nervous system and other mammalian nervous system is relatively simple,clear cell development system analysis.MADD-4 encoding three isoform MADD-4A,B and C.The subtypes of A and C protein amino acid sequence is long,called MADD-4L,and the amino acid sequence of B protein of subtype is short called MADD-4S.We use the madd-4 related mutants,monitoring online from L1 in different time period of synaptic development,we found that all the two subunits of madd-4 deletion in the case,the process of the elegans synaptic remodeling in advance.The loss of madd-4L and madd-4S alone is no difference with wild type phenotype.In order to further analyze this phenomenon,we combine the classic on the nematode was studied in the L1 period of synaptic remodeling related signaling pathways,MADD-4 protein and the regulation of L1 in the period of nematode synaptic remodeling.Lin-14 is the earliest discovered heterochronic gene,it control of space and time in the process of development,determines the direction of cell development,so as to ensure the correct positioning of each organization and timely development.Oig-1 and other three unc-30,lin-14,unc-55 transcription factor is the signaling pathways regulating synaptic remodeling process of the nematode L1.In order to study whether madd-4 depends on this signal pathway,in unc-30 mutant background,quantitative analysis of fluorescence signal of madd-4L and madd-4S mutants in the strength of madd-4L and madd-4S in unc-30 mutant background fluorescence expression level decreased,indicating that the expression of madd-4L and madd-4S transcription factor unc-30 regulating nematode larvae in the period of L1.Based on the above study,we compared wild-type and madd-4 mutant nematode has a time difference in the synaptic remodeling process,madd-4 mutant synaptic remodeling ahead of time,and no significant changes in madd-4L and madd-4S mutants of synaptic remodeling in time.At the same time,madd-4 is the transcriptional regulation of transcription factor unc-30 in synaptic remodeling process,the expression of madd-4L and madd-4S L1 during the period of nematode larvae.This study illustrates the extracellular matrix protein MADD-4 regulates DD neuronal remodeling mechanism for studying the mechanism of synaptic remodeling further identified.