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

First Author  Schaller S Year  2017
Journal  Proc Natl Acad Sci U S A Volume  114
Issue  12 Pages  E2486-E2493
PubMed ID  28270618 Mgi Jnum  J:318870
Mgi Id  MGI:6863314 Doi  10.1073/pnas.1615372114
Citation  Schaller S, et al. (2017) Novel combinatorial screening identifies neurotrophic factors for selective classes of motor neurons. Proc Natl Acad Sci U S A 114(12):E2486-E2493
abstractText  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 CNTFRalpha; and Artemin acts as the first survival factor for parasympathetic preganglionic motor neurons through GFRalpha3/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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