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

Significance

Neurotrophic factors are endogenous survival factors for developing neurons during their programmed cell death, and represent therapeutic candidates in several neurodegenerative diseases. Studies in the developing spinal cord suggest that neurotrophic factors promote the survival of motor neurons in a combinatorial manner. To better understand this, we systematically assayed pairwise combinations of neurotrophic factors (NTFs) on highly standardized motor neuron cultures prepared by a unique FACS technique. Our data unravel potent additivity of three neurotrophic factors due to their specific survival effects on distinct classes of motor neurons innervating different targets. Further analyses are required to better understand combinatorial NTF effects in adulthood and to define optimized NTF combinations for degenerative motor neuron diseases.