In:
eLife, eLife Sciences Publications, Ltd, Vol. 2 ( 2013-09-10)
Abstract:
Pluripotent stem cells have the potential to become most of the cell types that make up an organism. However, the signals that trigger these cells to turn into neurons rather than lung cells or muscle cells, for example, are not fully understood. Proteins called growth factors are known to have a role in this process, as are transcription factors, but it is not clear if other factors are also involved. In an attempt to identify additional mechanisms that could contribute to the formation of neurons, Sun et al. screened more than 2,000 small molecules for their ability to transform mouse pluripotent stem cells into neurons in cell culture. Surprisingly, they found that a compound called selamectin, which is used to treat parasitic flatworm infections, also triggered stem cells to turn into neurons. Selamectin works by blocking a particular type of ion channel in flatworms, but this ion channel is not found in vertebrates, which means that selamectin must be promoting the formation of neurons in mice via a different mechanism. Given that a drug related to selamectin is known to act on a subtype of receptors for the neurotransmitter GABA, Sun et al. wondered whether these receptors—known as GABAA receptors—might also underlie the effects of selamectin. Consistent with this idea, drugs that increased GABAA activity stimulated the formation of neurons, whereas drugs that reduced GABAA function blocked the effects of selamectin. In addition, Sun et al. showed that selamectin triggers human embryonic stem cells to become neurons, and that it also promotes the formation of new neurons in developing zebrafish in vivo. As well as revealing an additional mechanism for the formation of neurons from stem cells, the screening technique introduced by Sun et al. could help to identify further pro-neuronal molecules, which could aid the treatment of neurodevelopmental and neurodegenerative disorders.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.00508.001
DOI:
10.7554/eLife.00508.002
DOI:
10.7554/eLife.00508.003
DOI:
10.7554/eLife.00508.004
DOI:
10.7554/eLife.00508.005
DOI:
10.7554/eLife.00508.006
DOI:
10.7554/eLife.00508.007
DOI:
10.7554/eLife.00508.008
DOI:
10.7554/eLife.00508.009
DOI:
10.7554/eLife.00508.010
DOI:
10.7554/eLife.00508.011
DOI:
10.7554/eLife.00508.012
DOI:
10.7554/eLife.00508.013
DOI:
10.7554/eLife.00508.014
DOI:
10.7554/eLife.00508.015
DOI:
10.7554/eLife.00508.016
DOI:
10.7554/eLife.00508.017
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2013
detail.hit.zdb_id:
2687154-3
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