Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model
- PMID: 17435754
- PMCID: PMC3139463
- DOI: 10.1038/nn1885
Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model
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.
Figures





Comment in
-
ALS: astrocytes move in as deadly neighbors.Nat Neurosci. 2007 May;10(5):535-7. doi: 10.1038/nn0507-535. Nat Neurosci. 2007. PMID: 17453052 No abstract available.
-
Astrocytes usurp neurons as a disease focus.Nat Neurosci. 2019 Apr;22(4):512-513. doi: 10.1038/s41593-019-0367-6. Nat Neurosci. 2019. PMID: 30858602 No abstract available.
References
-
- Boillee S, Vande Velde C, Cleveland DW. ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron. 2006;52:39–59. - PubMed
-
- Brown RH., Jr. Amyotrophic lateral sclerosis. Insights from genetics. Arch. Neurol. 1997;54:1246–1250. - PubMed
-
- Cole N, Siddique T. Genetic disorders of motor neurons. Semin. Neurol. 1999;19:407–418. - PubMed
-
- Rosen DR, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;362:59–62. - PubMed
-
- Gurney ME, et al. Motor neuron degeneration in mice that express a human Cu/Zn superoxide dismutase mutation. Science. 1994;264:1772–1775. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Miscellaneous