title: Novel combinatorial screening identifies neurotrophic factors for selective classes of motor neurons.
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.
authors.affiliation: Institut de Neurosciences de la Timone, UMR 7289 CNRS, Aix-Marseille University, 13005 Marseille, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Schaller
authors.affiliation: Institut de Neurosciences de la Timone, UMR 7289 CNRS, Aix-Marseille University, 13005 Marseille, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Buttigieg
authors.affiliation: Institut de Neurosciences de la Timone, UMR 7289 CNRS, Aix-Marseille University, 13005 Marseille, France.
authors.forename: Alysson
authors.initials: A
authors.lastname: Alory
authors.affiliation: Institut de Neurosciences de la Timone, UMR 7289 CNRS, Aix-Marseille University, 13005 Marseille, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jacquier
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), CNRS, INSERM, Aix-Marseille University, 13288 Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Barad
authors.affiliation: Genentech Inc., South San Francisco, CA 94080.
authors.forename: Mark
authors.initials: M
authors.lastname: Merchant
authors.affiliation: Institut Curie, Translational Research Department, Genomic Platform, PSL Research University, 75248 Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Gentien
authors.affiliation: GenoSplice Technology, Institut du Cerveau et de la Moëlle (ICM), Hôpital Pitié Salpêtrière, 75013 Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: de la Grange
authors.affiliation: Institut de Neurosciences de la Timone, UMR 7289 CNRS, Aix-Marseille University, 13005 Marseille, France; georg.haase@univ-amu.fr.
authors.forename: Georg
authors.initials: G
authors.lastname: Haase
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism*; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D053670:Syndecan-3 / Q000235:genetics / Q000378:metabolism
chemical_list: C116599:Artn protein, mouse; D020934:Ciliary Neurotrophic Factor; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit; C494994:Gfra3 protein, mouse; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009419:Nerve Tissue Proteins; C508302:Sdc3 protein, mouse; D053670:Syndecan-3; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met
keywords: Artemin; fluorescence-activated cell sorting; motor neuron; neurotrophic factor; screening