This hypothesis was elegantly tested by Son et al. who attempted to generate iN cells with motor neuron identity directly from fibroblasts (Son et al., 2011) (Figure 1). Starting out with a fairly large pool of transcription factors critical for motor neuron specification, they eventually found that four (Lhx3, Hb9, Isl1 and Ngn2) in combination with the BAM factors generated Hb9-positive neurons with an efficiency of up to 10% from MEFs. Gene expression analyses indicated that these induced motor neuronal (iMN) cells resemble the transcription profiles of embryonic and ESC-derived motor neurons. Besides displaying electrophysiological properties akin to motor neurons, these iMN cells also formed functional synaptic connections with myotubes. When transplanted to the developing chick spinal cord, most of the iMN cells were engrafted in the ventral horn of the spinal with axons projecting into the ventral roots. In addition, the cells behaved similarly to ESC-derived motor neurons in disease conditions. When cultured with glia carrying the G93A mutation in the Superoxide dismutase (Sod1) gene, a mutation found in familial forms of amyotrophic lateral sclerosis (ALS), the survival of
