Loss of tau results in defects in photoreceptor development and progressive neuronal degeneration in Drosophila

Bonnie J. Bolkan, Doris Kretzschmar

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Accumulations of Tau, a microtubule-associated protein (MAP), into neurofibrillary tangles is a hallmark of Alzheimer's disease and other tauopathies. However, the mechanisms leading to this pathology are still unclear: the aggregates themselves could be toxic or the sequestration of Tau into tangles might prevent Tau from fulfilling its normal functions, thereby inducing a loss of function defect. Surprisingly, the consequences of losing normal Tau expression in vivo are still not well understood, in part due to the fact that Tau knockout mice show only subtle phenotypes, presumably due to the fact that mammals express several MAPs with partially overlapping functions. In contrast, flies express fewer MAP, with Tau being the only member of the Tau/MAP2/MAP4 family. Therefore, we used Drosophila to address the physiological consequences caused by the loss of Tau. Reducing the levels of fly Tau (dTau) ubiquitously resulted in developmental lethality, whereas deleting Tau specifically in neurons or the eye caused progressive neurodegeneration. Similarly, chromosomal mutations affecting dTau also caused progressive degeneration in both the eye and brain. Although photoreceptor cells initially developed normally in dTau knockdown animals, they subsequently degenerated during late pupal stages whereas weaker dTau alleles caused an age-dependent defect in rhabdomere structure. Expression of wild type human Tau partially rescued the neurodegenerative phenotype caused by the loss of endogenous dTau, suggesting that the functions of Tau proteins are functionally conserved from flies to humans.

Original languageEnglish (US)
Pages (from-to)1210-1225
Number of pages16
JournalDevelopmental Neurobiology
Volume74
Issue number12
DOIs
StatePublished - Dec 1 2014

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Keywords

  • Drosophila
  • Eye development
  • Neurodegeneration
  • Tau

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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