The study investigates the potential of using inductive signals and transcription factors involved in motor neuron (MN) generation to direct embryonic stem (ES) cells towards an MN fate. The researchers found that developmentally relevant signaling factors can induce mouse ES cells to differentiate into spinal progenitor cells, which subsequently develop into MNs. These ES cell-derived MNs can integrate into the embryonic spinal cord, extend axons, and form synapses with target muscles. The findings suggest that normal developmental pathways can be harnessed to direct ES cells to form specific classes of central nervous system (CNS) neurons, opening up possibilities for treating neurodegenerative diseases and spinal cord injuries. The study also highlights the importance of retinoic acid (RA) and sonic hedgehog (Shh) signaling in the differentiation process, and demonstrates the feasibility of applying these insights to generate other predefined classes of CNS neurons.The study investigates the potential of using inductive signals and transcription factors involved in motor neuron (MN) generation to direct embryonic stem (ES) cells towards an MN fate. The researchers found that developmentally relevant signaling factors can induce mouse ES cells to differentiate into spinal progenitor cells, which subsequently develop into MNs. These ES cell-derived MNs can integrate into the embryonic spinal cord, extend axons, and form synapses with target muscles. The findings suggest that normal developmental pathways can be harnessed to direct ES cells to form specific classes of central nervous system (CNS) neurons, opening up possibilities for treating neurodegenerative diseases and spinal cord injuries. The study also highlights the importance of retinoic acid (RA) and sonic hedgehog (Shh) signaling in the differentiation process, and demonstrates the feasibility of applying these insights to generate other predefined classes of CNS neurons.