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dc.contributor.advisor Sherwood, Nina T en_US
dc.contributor.author Stewart, Andrea en_US
dc.date.accessioned 2012-01-10T16:00:17Z
dc.date.available 2013-01-04T05:30:14Z
dc.date.issued 2011 en_US
dc.identifier.uri http://hdl.handle.net/10161/5032
dc.description Dissertation en_US
dc.description.abstract <p>Dendrite shape is a defining component of neuronal function. Yet, the mechanisms specifying diverse dendritic morphologies, and the extent to which their functioning depends on these morphologies, remain unclear. Here, we demonstrate a dendrite-specific requirement for the microtubule severing protein Katanin p60-like 1 (Kat-60L1) in regulating the elaborate branch morphology and nocifensive functions of Drosophila melanogaster larval class IV dendritic arborization (da) neuron dendrites. Through genetic loss of function analysis we show that loss of kat-60L1 reduced dendrite branching and process length, particularly during a period of normally extensive growth. This morphological defect was paralleled by a reduction in nocifensive responsiveness mediated by these neurons, indicating a tight correlation between neuronal function and the full extent of the dendritic arbor. To understand the mechanism underlying Kat-60L1's effects, we used in vivo imaging of the microtubule plus-end binding protein EB1, and found fewer polymerizing microtubules within mutant dendrites. Kat-60L1 thus promotes microtubule growth within class IV dendrites to establish the full arbor complexity and nocifensive functions of these neurons. </p><p>Although reduction of the related microtubule severing protein Spastin also compromised class IV dendrite arborization and nocifensive responses, microtubule polymerization in dendrites was unchanged in spastin mutants, and behavioral defects arose from generally compromised neuronal excitation. Kat-60L1 and Spastin thus function in distinct neuronal compartments to establish the complex dendritic morphology and sensory functions of class IV da neurons via distinct mechanisms of microtubule regulation. Whereas Spastin regulates stable microtubules affecting both pre- and post-synaptic compartments of these neurons, Kat-60L1 function is required specifically in dendrites to promote their complex arborization through the addition of growing microtubule numbers. Double mutant analysis demonstrated that Kat-60L1 and Spastin function antagonistically to promote dendritic aborization, likely involving other molecular players involved in regulating the microtubule cytoskeleton. Lastly, we identified Mi-2 as a transcriptional regulator of both kat-60L1 and spastin and show a genetic interaction between mi-2 and kat-60L1 in the class IV dendritic arbor, demonstrating that Mi-2 antagonizes Kat-60L1 function, possibly through the parallel upregulation of spastin. These data support a key role for the differential utilization of microtubule severing in generating distinct neuronal morphologies and subsequent function.</p> en_US
dc.subject Biology en_US
dc.subject Cellular biology en_US
dc.subject dendrite en_US
dc.subject microtubule en_US
dc.subject nociception en_US
dc.subject severing en_US
dc.title Microtubule Severing Protein Regulation of Sensory Neuron Form and Function in Drosophila melanogaster en_US
dc.type Dissertation en_US
dc.department Biology en_US
duke.embargo.months 12 en_US

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