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Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):E2486-E2493. doi: 10.1073/pnas.1615372114. Epub 2017 Mar 7.

Novel combinatorial screening identifies neurotrophic factors for selective classes of motor neurons.

Author information

1
Institut de Neurosciences de la Timone, UMR 7289 CNRS, Aix-Marseille University, 13005 Marseille, France.
2
Centre d'Immunologie de Marseille-Luminy (CIML), CNRS, INSERM, Aix-Marseille University, 13288 Marseille, France.
3
Genentech Inc., South San Francisco, CA 94080.
4
Institut Curie, Translational Research Department, Genomic Platform, PSL Research University, 75248 Paris, France.
5
GenoSplice Technology, Institut du Cerveau et de la Moëlle (ICM), Hôpital Pitié Salpêtrière, 75013 Paris, France.
6
Institut de Neurosciences de la Timone, UMR 7289 CNRS, Aix-Marseille University, 13005 Marseille, France; georg.haase@univ-amu.fr.

Abstract

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 CNTFRα; and Artemin acts as the first survival factor for parasympathetic preganglionic motor neurons through GFRα3/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.

KEYWORDS:

Artemin; fluorescence-activated cell sorting; motor neuron; neurotrophic factor; screening

PMID:
28270618
PMCID:
PMC5373341
DOI:
10.1073/pnas.1615372114
[Indexed for MEDLINE]
Free PMC Article

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