Abstract

Here we report an in vitro model system for studying the molecular and cellular mechanisms that underlie the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Embryonic stem cells (ESCs) derived from mice carrying normal or mutant transgenic alleles of the human SOD1 gene were used to generate motor neurons by in vitro differentiation. These motor neurons could be maintained in long-term coculture either with additional cells that arose during differentiation or with primary glial cells. Motor neurons carrying either the nonpathological human SOD1 transgene or the mutant SOD1^G93A allele showed neurodegenerative properties when cocultured with SOD1^G93A glial cells. Thus, our studies demonstrate that glial cells carrying a human SOD1^G93A mutation have a direct, non–cell autonomous effect on motor neuron survival. More generally, our results show that ESC-based models of disease provide a powerful tool for studying the mechanisms of neural degeneration. These phenotypes displayed in culture could provide cell-based assays for the identification of new ALS drugs.

1. The Stowers Medical Institute, the Harvard Stem Cell Institute. Harvard University, 7 Divinity Ave., Cambridge, Massachusetts 02138, USA.
2. the Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Ave., Cambridge, Massachusetts 02138, USA.
3. Perugia Universitâ Piazza dell' Universitâ 1, Perugia 06100, Italy.
4. These authors contributed equally to this work.

Correspondence to: Tom Maniatis² e-mail: maniatis@mcb.harvard.edu

Correspondence to: Kevin Eggan^1,2 e-mail: eggan@mcb.harvard.edu

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

NPG Journals

by Subject Area

• Chemistry

  • Chemistry
  • Drug discovery
  • Biotechnology
  • Materials
  • Methods & Protocols

• Clinical Practice & Research

  • Cancer
  • Cardiovascular medicine
  • Dentistry
  • Endocrinology
  • Gastroenterology & Hepatology
  • Methods & Protocols
  • Pathology & Pathobiology
  • Urology

• Earth & Environment

  • Earth sciences
  • Evolution & Ecology

• Life sciences

  • Biotechnology
  • Cancer
  • Development
  • Drug discovery
  • Evolution & Ecology
  • Genetics
  • Immunology
  • Medical research
  • Methods & Protocols
  • Microbiology
  • Molecular cell biology
  • Neuroscience
  • Pharmacology
  • Systems biology

• Physical sciences

  • Physics
  • Materials

by A - Z Index