Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 12, Pages E2486-E2493Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1615372114
Keywords
neurotrophic factor; motor neuron; screening; fluorescence-activated cell sorting; Artemin
Categories
Funding
- Association Francaise contre les Myopathies (AFM)
- Agence Nationale pour la Recherche (ANR)
- ERANET Neuron
- INSERM
- Aix-Marseille University
- ANR
- Fondation pour la Recherche Medicale (FRM)
- AFM
- INSERM/Region Provence Alpes Cotes d'Azur
- FRM
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Numerous neurotrophic factors promote the survival of developing motor neurons but their combinatorial actions remain poorly understood; to address this, we here screened 66 combinations of 12 neurotrophic factors on pure, highly viable, and standardized embryonic mouse motor neurons isolated by a unique FACS technique. We demonstrate potent, strictly additive, survival effects of hepatocyte growth factor (HGF), ciliary neurotrophic factor (CNTF), and Artemin through specific activation of their receptor complexes in distinct subsets of lumbar motor neurons: HGF supports hindlimb motor neurons through c-Met; CNTF supports subsets of axial motor neurons through CNTFR alpha; and Artemin acts as the first survival factor for parasympathetic preganglionic motor neurons through GFRa3/Syndecan-3 activation. These data show that neurotrophic factors can selectively promote the survival of distinct classes of embryonic motor neurons. Similar studies on postnatal motor neurons may provide a conceptual framework for the combined therapeutic use of neurotrophic factors in degenerative motor neuron diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy, and spinobulbar muscular atrophy.
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