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Transcriptional And Posttranscriptional Regulation Of GABAergic D Motor Neurons In Caenorhabditis Elegans

Posted on:2014-04-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:L F MengFull Text:PDF
GTID:1220330425473285Subject:Biophysics
Abstract/Summary:PDF Full Text Request
In mammals, synaptic remodeling occurs in almost all circuits. However, much less is known about the mechanisms of synaptic refinement. Caenorhabditis elegans is a valuable model system to study this question in developmental neurobiology, because the nervous system of C. elegans has only302neurons and the lineage of C. elegans is well illustrated. In this study, we analyzed the genes involved in developmentally programmed remodeling of GABAergic neurons and investigated the mechanisms that pattern synaptic plasticity.GABA is an important neurotransmitter which functions in inhibitory synapses in C. elegans. D-type GABA neurons are divided into6DD and13VD motor neurons which innervate the dorsal and ventral body muscles respectively. During the first larval stage, the DD GABAergic neurons undergo a remodeling process that the component of presynaptic shifts from ventral to dorsal side. There are two key factors function in this program, UNC-30and UNC-55. UNC-30is responsible for the generation of D motor neurons and UNC-55is required to distinguish these two distinct D motor neurons.We predicted21genes which are regulated by UNC-30and UNC-55. In the follow experiment, we identified9genes which expressed in D motor neurons and regulated by UNC-30. Most of these genes are members of JNK family, previous study and the yeast two-hybird data suggested that they functioned in a pathway to regulate the development of D motor neurons.What’s more, a microRNA is also found to be involved in this pathway. It is controled by UNC-30meanwhile it down regulates UNC-30through binding with its3:UTR. Therefore, a feed back loop in this pathway controls the expression of UNC-30. Worms that expresses more unc-30exhibit defect in locomotion.In summary, we identified a JNK pathway that function in the development of D motor neurons, and a microRNA that function by suppressing the expression of UNC-30.In the long history of evolutionary process, the main stress for the evolution is from the struggle between predators and prey. Here we introduce an example that the E.coli. generates RNA to affect the physiology of C. elegans. Both OxyS and DsrA are mutant bacteria that were isolated from nature environment. The mutation of Oxys generates a microRNA which can silence the expression of che-2resulting in the defect in foraging. So the OxyS gain the ability of defense itself from C. elegans, however the growth rate of OxyS is slower comparing to wild type. The mutation of DsrA lose the ability of generating a RNA which can suppress the expression of F42G9.6. The growth rate of DsrA is higher than wild type. However, the worm could live longer if they live on DsrA. In conclusion, different nature environment affect the evolution.
Keywords/Search Tags:Caenorhabditis elegans, GABAergic neurons, Remodel, MicroRNA, Interspecies
PDF Full Text Request
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