UCSF

Despite their key role in neuronal function, current understanding of dendrite development and regeneration are lacking. We focused on the class IV dendritic arborization (c4da) neuron of the Drosophila sensory system to address aspects of dendrite development and regeneration due to the complex dendritic arbor and peripheral location of these neurons. Although molecular motors are known to play a role in the development of the dendritic arbor, there was not a comprehensive understanding of kinesins in dendrite development. Therefore, a screen for kinesins which regulate dendritic arbor complexity was performed. Candidates for further study were identified. Aspects of dendrite development in adulthood were also examined, including the function of c4da neuron in the adult abdomen and the source of extracellular matrix in the abdomen. The focus of this work is on the ability of neurons to regenerate dendrites. This study characterizes the structural and functional capacity for dendrite regeneration in vivo in adult animals and examines the effect of neuronal maturation on dendrite regeneration. which has a dendritic arbor that undergoes dramatic remodeling during the first 3 d of adult life and then maintains a relatively stable morphology thereafter. Using a laser severing paradigm, we monitored regeneration after acute and spatially restricted injury. We found that the capacity for regeneration was present in adult neurons but diminished as the animal aged. Regenerated dendrites recovered receptive function. Furthermore, we found that the regenerated dendrites show preferential alignment with the extracellular matrix (ECM). Finally, inhibition of ECM degradation by inhibition of matrix metalloproteinase 2 (Mmp2) to preserve the extracellular environment characteristics of young adults led to increased dendrite regeneration. These results demonstrate that dendrites retain regenerative potential throughout adulthood and that regenerative capacity decreases with aging.