A Drosophila model for TDP-43 proteinopathy

Yan Li*, Payal Ray, Elizabeth J. Rao, Chen Shi, Weirui Guo, Xiaoping Chen, Elvin A. Woodruff, Kazuo Fushimi, Jane Y. Wu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

228 Scopus citations


Neuropathology involving TAR DNA binding protein-43 (TDP-43) has been identified in a wide spectrum of neurodegenerative diseases collectively named as TDP-43 proteinopathy, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). To testwhether increasedexpressionofwide- typehuman TDP-43(hTDP-43) may cause neurotoxicity in vivo, we generated transgenic flies expressinghTDP-43invariousneuronalsubpopulations. Expressionin the fly eyes of the full-length hTDP-43, but not a mutant lacking its amino-terminal domain, led to progressive loss of ommatidia with remarkable signs of neurodegeneration. Expressing hTDP-43 inmushroom bodies (MBs) resulted in dramatic axon losses and neuronal death. Furthermore, hTDP-43 expressioninmotor neurons led to axon swelling, reductionin axonbranches andbouton numbers, andmotor neuron loss together with functional deficits. Thus, our transgenic flies expressing hTDP-43 recapitulate important neuropathological and clinical features of human TDP-43 proteinopathy, providing a powerful animal model for this group of devastating diseases. Our study indicates that simply increasing hTDP-43 expressionis sufficient to cause neurotoxicity in vivo, suggesting that aberrant regulation of TDP-43 expression or decreased clearance of hTDP-43may contribute to the pathogenesis of TDP-43 proteinopathy.

Original languageEnglish (US)
Pages (from-to)3169-3174
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Feb 16 2010


  • Amyotrophic lateral sclerosis
  • Animal model
  • RNA binding protein

ASJC Scopus subject areas

  • General


Dive into the research topics of 'A Drosophila model for TDP-43 proteinopathy'. Together they form a unique fingerprint.

Cite this