A Database of Drosophila Genes & Genomes

FB2013_03, released May 7th, 2013
 

Reference Report

Reference
Citation Nishimura, Y., Yalgin, C., Akimoto, S., Doumanis, J., Sasajima, R., Nukina, N., Miyakawa, H., Moore, A.W., Morimoto, T. (2010). Selection of Behaviors and Segmental Coordination During Larval Locomotion Is Disrupted by Nuclear Polyglutamine Inclusions in a New Drosophila Huntington's Disease-Like Model.  J. Neurogenet. 24(4): 194--206. (Export to RIS)
FlyBase ID FBrf0212327
Publication Type Research paper
PubMed ID 21087194
PubMed Abstract Huntington's disease is an autosomal dominant neurodegenerative disorder that is caused by abnormal expansion of a polyglutamine tract in the huntingtin protein, resulting in intracellular aggregate formation and neurodegeneration. How neuronal cells are affected by such a polyglutamine tract expansion remains obscure. To dissect the ways in which polyglutamine expansion can cause neural dysfunction, the authors generated Drosophila transgenic strains expressing either a nuclear targeted or cytoplasmic form of pathogenic (NHtt-152Q(NLS), NHtt-152Q), or nonpathogenic (NHtt-18Q(NLS), NHtt-18Q) N-terminal human huntingtin. These proteins were expressed in the dendritic arborization neurons of the larval peripheral nervous system and their effects on neuronal survival, morphology, and larval locomotion were examined. The authors found that NHtt-152Q(NLS) larvae had altered dendrite morphology and larval locomotion, whereas NHtt-152Q, NHtt-18Q(NLS), and NHtt-18Q larvae did not. Furthermore, the authors examined the physiological defect underlying this disrupted larval locomotion in detail by recording spontaneous ongoing segmental nerve activity. NHtt-152Q(NLS) larvae displayed uncoordinated activity between anterior and posterior segments. Moreover, anterior segments had shorter bursts and longer interburst intervals in NHtt-152Q(NLS) larvae than in NHtt-18Q(NLS) larvae, whereas posterior segments had longer bursts and shorter interburst intervals. These results suggest that the pathogenic protein disrupts neuron function without inducing cell death, and describe how this dysfunction leads to a locomotor defect. These results also suggest that sensory inputs are necessary for the coordination of anterior and posterior body parts during locomotion. From these analyses the authors show that examination of motor behaviors in the Drosophila larvae is a powerful new model to dissect non-cell-lethal mechanisms of mutant Htt toxicity.
DOI 10.3109/01677063.2010.514367
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Language of Publication English
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Publication Type Journal
Abbreviation J. Neurogenet.
Title Journal of Neurogenetics
Publication Year 1983-
ISBN/ISSN 0167-7063
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