A second critical neuronal subtype is spinal motor neurons. Son and coworkers used seven factors (BAM factors plus Lhx3, Hb9, Isl1, and Ngn2) for mouse fibroblasts to generate cells similar to motor neurons termed induced motor neuronal (iMN) cells. A seventh factor NeuroD1 needed to be added to convert human fibroblast-like cells derived from human embryonic stem (ES) cells [36]. Mouse iMN cells shared similar electrophysiological and gene expression properties with motor neurons derived from ES cells and were able to innervate cultured myotubes in a curare-dependent manner, a specific blocker of acetylcholine receptors known to mediate synaptic transmission at the neuronal-muscular junction. The iMN cells were also shown to phenocopy disease traits. Cells expressing the SOD1G93A mutant form of SOD1, a mutation causing amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, displayed similar survival defects as primary motor neurons. Similarly, wild type iMN cells co-cultured with mutant glia were less viable compared to co-cultures with wild type glia as expected.
