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Tissue-specific transcription of the neuronal gene Lim3 affects Drosophila melanogaster lifespan and locomotion

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Abstract

The identity of neuronal cell types is established and maintained by the expression of neuronal genes coding for ion channels, neurotransmitters, and neuropeptides, among others. Some of these genes have been shown to affect lifespan; however, their role in lifespan control remains largely unclear. The Drosophila melanogaster gene Lim3 encodes a transcription factor involved in complicated motor neuron specification networks. We previously identified Lim3 as a candidate gene affecting lifespan. To obtain direct evidence of the involvement of Lim3 in lifespan control, Lim3 overexpression and RNAi knockdown were induced in the nervous system and muscles of Drosophila using the GAL4-UAS binary system. We demonstrated that Lim3 knockdown in the nervous system increased survival at an early age and that Lim3 knockdown in muscles both increased survival at an early age and extended median lifespan, directly establishing the involvement of Lim3 in lifespan control. Lim3 overexpression in nerves and muscles was deleterious and led to lethality and decreased lifespan, respectively. Lim3 misexpression in both nerves and muscles increased locomotion regardless of changes in lifespan, which indicated that the effects of Lim3 on lifespan and locomotion can be uncoupled. Decreased synaptic activity was observed in the neuromuscular junctions of individuals with Lim3 overexpression in muscles, in association with decreased lifespan. However, no changes in NMJ activity were associated with the positive shift in locomotion observed in all misexpression genotypes. Our data suggested that modifications in the microtubule network may be induced by Lim3 misexpression in muscles and cause an increase in locomotion.

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Acknowledgements

Flies obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. We thank the TRiP at Harvard Medical School (NIH/NIGMS R01-GM084947) for providing the transgenic RNAi fly stocks used in this study. We also thank Addgene for providing the pBID-UASC plasmid and BestGene Inc. for creating transgenic flies with the additional Lim3 copy. We are grateful to American Journal Experts (http://www.aje.com/) for English editing services. We are also grateful for the unknown reviewers for their helpful criticism and suggestions. This work was supported by the Presidium of the Russian Academy of Sciences Program “Biodiversity of natural systems” and by Russian Foundation for Basic Research grant 15-04-05797-a to Elena G. Pasyukova.

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Authors and Affiliations

  1. Institute of Molecular Genetics of the Russian Academy of Sciences, Kutchatov Sq. 2, Moscow, Russia, 123182

    Olga Y. Rybina, Ekaterina R. Veselkina, Alexander V. Symonenko, Anna V. Krementsova, Natalia V. Roshina & Elena G. Pasyukova

  2. Federal State-Financed Educational Institution of Higher Professional Education, Moscow State Pedagogical University, M. Pirogovskaya Str. 1/1, Moscow, Russia, 119991

    Olga Y. Rybina

  3. B. P. Konstantinov Petersburg Nuclear Physics Institute, National Research Centre “Kurchatov Institute”, Orlova Roscha, Gatchina, Russia, 1888300

    Svetlana V. Sarantseva, Olga I. Bolschakova & Elena V. Ryabova

  4. N. M. Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences, Kosygin St. 4, Moscow, Russia, 119334

    Anna V. Krementsova

  5. Vavilov Institute of General Genetics, Russian Academy of Sciences, Gubkin 3, Moscow, Russia, 119991

    Natalia V. Roshina

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  1. Olga Y. Rybina
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  2. Svetlana V. Sarantseva
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  3. Ekaterina R. Veselkina
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Rybina, O.Y., Sarantseva, S.V., Veselkina, E.R. et al. Tissue-specific transcription of the neuronal gene Lim3 affects Drosophila melanogaster lifespan and locomotion. Biogerontology 18, 739–757 (2017). https://doi.org/10.1007/s10522-017-9704-x

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