Constructing and Maintaining the Nervous System: Molecular Insights Underlying Neuronal Architecture, Synaptic Development, and Synaptic Maintenance Using C. elegans
Authors
Oliver, DevynFaculty Advisor
Michael M. FrancisAcademic Program
NeuroscienceDocument Type
Doctoral DissertationPublication Date
2021-03-12Keywords
neurosciencedendritic spine
C. elegans
synapse
neuron
development
maintenance
Developmental Neuroscience
Molecular and Cellular Neuroscience
Metadata
Show full item recordAbstract
In the nervous system, billions of neurons undergo a multistep process to establish functional circuits. This entails accurate extension of dendritic and axonal processes and coordinated efforts of pre- and postsynaptic neurons to form synaptic connections. Although many axon guidance molecules and synaptic organizers have been identified, the molecular redundancy and the vast number of synapses in the brain has complicated attempts to define their precise roles. In order to understand the molecular mechanisms that encompass these processes, my studies utilize the genetic strengths and cellular precision available in Caenorhabditis elegans for in vivo investigations of nervous system development. In this work, I unravel cell-specific requirements for the transmembrane receptor integrin in regulating developmental axon guidance of GABAergic motor neurons. Furthermore, I address important questions about mechanisms of synapse formation and maintenance using a novel dendritic spine model in C. elegans. Using high resolution microscopy, I find that the formation of immature presynaptic vesicles and postsynaptic receptors are established prior to the outgrowth of dendritic spines at nascent synapses. During this early period of synapse formation, the kinesin-3 family protein UNC-104/KIF1A transports a transsynaptic adhesion molecule neurexin/NRX-1 to developing active zones, in order to maintain postsynaptic receptors and dendritic spines in the mature circuit. In the absence of nrx-1, spines initially form normally but collapse following their extension. These findings demonstrate that presynaptic NRX-1 is required to maintain postsynaptic structures. Together my work provides new insights into molecular mechanisms that define spatiotemporal characteristics of nervous system development and the maintenance of connectivity.DOI
10.13028/rxrc-6f03Permanent Link to this Item
http://hdl.handle.net/20.500.14038/31352Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/rxrc-6f03