Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Subject collections
    • Interviews
    • Alerts
  • About us
    • About DMM
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Workshops and Meetings
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • Outstanding paper prize
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Alerts
  • Contact
    • Contact DMM
    • Advertising
    • Feedback
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

User menu

  • Log in

Search

  • Advanced search
Disease Models & Mechanisms
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

supporting biologistsinspiring biology

Disease Models & Mechanisms

Advanced search

RSS   Twitter   Facebook   YouTube

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Subject collections
    • Interviews
    • Alerts
  • About us
    • About DMM
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Workshops and Meetings
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • Outstanding paper prize
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Alerts
  • Contact
    • Contact DMM
    • Advertising
    • Feedback
Research Article
Motor neurons and glia exhibit specific individualized responses to TDP-43 expression in a Drosophila model of amyotrophic lateral sclerosis
Patricia S. Estes, Scott G. Daniel, Abigail P. Mccallum, Ashley V. Boehringer, Alona S. Sukhina, Rebecca A. Zwick, Daniela C. Zarnescu
Disease Models & Mechanisms 2013 : dmm.010710 doi: 10.1242/dmm.010710 Published 8 March 2013
Patricia S. Estes
University of Arizona, Tucson, AZ 85721, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott G. Daniel
University of Arizona, Tucson, AZ 85721, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Abigail P. Mccallum
University of Arizona, Tucson, AZ 85721, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ashley V. Boehringer
University of Arizona, Tucson, AZ 85721, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alona S. Sukhina
University of Arizona, Tucson, AZ 85721, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rebecca A. Zwick
University of Arizona, Tucson, AZ 85721, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniela C. Zarnescu
University of Arizona, Tucson, AZ 85721, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & metrics
  • PDF
Loading

Summary

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by complex neuronal and glial phenotypes. Recently, RNA-based mechanisms have been linked to ALS via RNA-binding proteins such as TDP-43, which has been studied in vivo using models ranging from yeast to rodents. We have developed a Drosophila model of ALS based on TDP-43 that recapitulates several aspects of pathology, including motor neuron loss, locomotor dysfunction and reduced survival. Here we report the phenotypic consequences of expressing wild-type and four different ALS-linked TDP-43 mutations in neurons and glia. We show that TDP-43-driven neurodegeneration phenotypes are dose- and age-dependent. In motor neurons, TDP-43 appears restricted to nuclei, which are significantly misshapen due to mutant but not wild-type protein expression. In glia and in the developing neuroepithelium, TDP-43 associates with cytoplasmic puncta. TDP-43-containing RNA granules are motile in cultured motor neurons, although wild-type and mutant variants exhibit different kinetic properties. At the neuromuscular junction, the expression of TDP-43 in motor neurons versus glia leads to seemingly opposite synaptic phenotypes that, surprisingly, translate into comparable locomotor defects. Finally, we explore sleep as a behavioral readout of TDP-43 expression and find evidence of sleep fragmentation consistent with hyperexcitability, a suggested mechanism in ALS. These findings support the notion that although motor neurons and glia are both involved in ALS pathology, at the cellular level they can exhibit different responses to TDP-43. In addition, our data suggest that individual TDP-43 alleles utilize distinct molecular mechanisms, which will be important for developing therapeutic strategies.

  • Received August 10, 2012.
  • Accepted January 27, 2013.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms.

Next Article
Back to top
Next Article

This Issue

RSSRSS

 Download PDF

Email

Thank you for your interest in spreading the word on Disease Models & Mechanisms.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Motor neurons and glia exhibit specific individualized responses to TDP-43 expression in a Drosophila model of amyotrophic lateral sclerosis
(Your Name) has sent you a message from Disease Models & Mechanisms
(Your Name) thought you would like to see the Disease Models & Mechanisms web site.
Share
Motor neurons and glia exhibit specific individualized responses to TDP-43 expression in a Drosophila model of amyotrophic lateral sclerosis
Patricia S. Estes, Scott G. Daniel, Abigail P. Mccallum, Ashley V. Boehringer, Alona S. Sukhina, Rebecca A. Zwick, Daniela C. Zarnescu
Disease Models & Mechanisms 2013 : dmm.010710 doi: 10.1242/dmm.010710 Published 8 March 2013
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Motor neurons and glia exhibit specific individualized responses to TDP-43 expression in a Drosophila model of amyotrophic lateral sclerosis
Patricia S. Estes, Scott G. Daniel, Abigail P. Mccallum, Ashley V. Boehringer, Alona S. Sukhina, Rebecca A. Zwick, Daniela C. Zarnescu
Disease Models & Mechanisms 2013 : dmm.010710 doi: 10.1242/dmm.010710 Published 8 March 2013

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Alerts

Please log in to add an alert for this article.

Sign in to email alerts with your email address

Article navigation

  • Top
  • Article
  • Info & metrics
  • PDF

Related articles

Cited by...

More in this TOC section

  • Sporadic amyotrophic lateral sclerosis (SALS) – skeletal muscle response to cerebrospinal fluid from SALS patients in a rat model
  • Tumor xenograft modeling identifies TCF4/ITF2 loss associated with breast cancer chemoresistance
  • Synergistic anti-proliferative effect of mTOR inhibitor (rad001) plus gemcitabine on cholangiocarcinoma by decreasing choline kinase activity
Show more RESEARCH ARTICLE

Similar articles

Subject collections

  • Drosophila as a Disease Model

Other journals from The Company of Biologists

Development

Journal of Cell Science

Journal of Experimental Biology

Biology Open

Advertisement

Editor’s Choice – Altered expression of the Cdk5 activator-like protein, Cdk5α, causes neurodegeneration, in part by accelerating the rate of aging

By developing a comprehensive and quantitative metric for physiological age of Drosophila, Edward Giniger and colleagues show that a neurodegeneration mutant produces its effects in part by accelerating the absolute rate of aging.


First Person interviews 

Have you seen our interviews with the early-career first authors of our papers? Recently, we caught up with first authors Sarah Foriel, Henna Myllymäki and Mirja Niskanen, Wenqing Zhou, Rifdat Aoidi and Amy Irving.


Review – Metastasis in context: modeling the tumor microenvironment with cancer-on-a-chip approaches

In a new Review article, Jaap M. J. den Toonder and colleagues evaluate the recent contributions of cancer-on-a-chip models to our understanding of the tumor microenvironment and its role in the onset of metastasis. The authors also provide an outlook for future applications of this emerging technology.


DMM Conference Travel Grants

Are you an early career scientist with plans to attend a scientific meeting, conference, workshop or course relating to the areas of research covered by DMM? The next round of applications for DMM Conference Travel Grants closes on 4 May 2018. Find out more here and get your application in soon.


Why should you publish your next paper in DMM?

DMM aims to promote human health by encouraging collaboration between basic and clinical researchers, covering a diverse range of diseases, approaches and models. Our Editors are all active researchers in the field – your peers, colleagues and mentors, who know how much work has gone into every paper. Recently, we have introduced format-free submission, and we accept peer review reports from other journals, making submission as easy as possible for our authors. Send us your next great paper – publish with us and you'll be in good company.

Articles

  • Accepted manuscripts
  • Issue in progress
  • Latest complete issue
  • Issue archive
  • Archive by article type
  • Subject collections
  • Interviews
  • Alerts

About us

  • About DMM
  • Editors and Board
  • Editor biographies
  • Travelling Fellowships
  • Grants and funding
  • Workshops and Meetings
  • The Company of Biologists

For Authors

  • Submit a manuscript
  • Aims and scope
  • Presubmission enquiries
  • Article types
  • Manuscript preparation
  • Cover suggestions
  • Editorial process
  • Promoting your paper
  • Open Access
  • Biology Open transfer

Journal Info

  • Journal policies
  • Rights and permissions
  • Media policies
  • Reviewer guide
  • Alerts

Contact

  • Contact DMM
  • Advertising
  • Feedback

Twitter   YouTube   LinkedIn

© 2018   The Company of Biologists Ltd   Registered Charity 277992