Nguyen, Thi-Minh. Examination of alternative splice code of neurexins for synaptic specification. 2016, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_12031
Here, I report that by using bichromatic reporters, alternative splicing is differentially regulated between neuronal and non-neuronal cell populations and that the alternative splicing activity within a cell population can exhibit different levels of cell-to-cell variations. By profiling Nrxn mRNA repertoires in genetically-defined neuronal cell populations, I have identified highly divergent splice insert incorporation choices in two fundamentally different neurons populations in the hippocampus. Indeed, exon 21 which encodes for splice insert at alternative splice segment 4 (AS4) in Nrxn is predominantly incorporated in mRNA in Parvalbumin interneurons compared to excitatory Camk2 pyramidal neurons. Finally I investigated the function of Neurexin isoforms containing the exon 21 in vivo by conditionally deleting them in Parvalbumin interneurons population. Anatomical analyses indicated that synaptic density and vesicle docking were unaltered. However, mice in which isoforms containing splice insert at AS4 in Nrxn 1 and 3 were deleted, displayed an impaired short-term memory formation.
Thus, my study has provided evidences that alternative splicing regulation of Nrxn genes is genetically encoded and that deletion of cell-type specific isoforms impairs neuronal functions. This highlights the relevance of cell-type specific regulation of alternative splicing.
|Advisors:||Scheiffele, Peter and Arber, Silvia|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Scheiffele)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||1 Online-Ressource (127 Seiten)|
|Last Modified:||09 Feb 2017 10:22|
|Deposited On:||09 Feb 2017 10:22|
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