During neural development, coordinate regulation of cell-cycle exit and differentiation is essential for cell-fate specification, cell survival, and proper wiring of neuronal circuits. However, the molecules that direct these events remain poorly defined. In the developing spinal cord, the differentiation of motor neuron progenitors into postmitotic motor neurons is regulated by retinoid signaling. Here, we identify a retinoid-inducible gene, GDE2 (glycerophosphodiester phosphodiesterase 2), encoding a six-transmembrane protein that is necessary and sufficient to drive spinal motor neuron differentiation in vivo. A single amino acid mutation in the extracellular catalytic domain abolishes protein function. This reveals a critical role for glycerophosphodiester metabolism in motor neuron differentiation.
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