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Mol Brain. 2009 Sep 25;2:30. doi: 10.1186/1756-6606-2-30.

Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branching.

Author information

  • 1Gladstone Institute of Neurological Disease, and Department of Neurology, University of California, San Francisco, CA 94158, USA. ylu@gladstone.ucsf.edu

Abstract

BACKGROUND:

TDP-43 is an evolutionarily conserved RNA-binding protein implicated in the pathogenesis of frontotemporal dementia (FTD), sporadic and familial amyotrophic lateral sclerosis (ALS), and possibly other neurodegenerative diseases. In diseased neurons, TDP-43 is depleted in the nucleus, suggesting a loss-of-function pathogenic mechanism. However, the normal function of TDP-43 in postmitotic neurons is largely unknown.

RESULTS:

Here we demonstrate that overexpression of Drosophila TDP-43 (dTDP-43) in vivo significantly increases dendritic branching of sensory neurons in Drosophila larvae. Loss of dTDP-43 function, either in a genetic null mutant or through RNAi knockdown, decreased dendritic branching. Further genetic analysis demonstrated a cell-autonomous role for dTDP-43 in dendrite formation. Moreover, human TDP-43 (hTDP-43) promoted dendritic branching in Drosophila neurons, and this function was attenuated by mutations associated with ALS.

CONCLUSION:

These findings reveal an essential role for TDP-43 in dendritic structural integrity, supporting the notion that loss of normal TDP-43 function in diseased neurons may compromise neuronal connectivity before neuronal cell loss in FTD and ALS.

PMID:
19781077
[PubMed - indexed for MEDLINE]
PMCID:
PMC2762964
Free PMC Article
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