Single-stranded DNA binding proteins are required for LIM complexes to induce transcriptionally active chromatin and specify spinal neuronal identities.

LIM homeodomain factors regulate the development of many cell types. However, transcriptional coactivators that mediate their developmental function remain poorly defined. To address these, we examined how two related NLI-dependent LIM-complexes, which govern the development of spinal motor neurons and V2a-interneurons, activate the transcription in the embryonic spinal cord. We found that single-stranded DNA-binding proteins (Ssdps) are recruited to these LIM-complexes via NLI, and enhance their transcriptional activation potential. Ssdps are highly expressed in the neural tube and promote motor neuron differentiation in the embryonic spinal cord and P19 stem cells. Inhibition of Ssdp activity in mouse and chick embryos suppresses the generation of motor neurons and V2a-interneurons. Furthermore, Ssdps recruit histone modifying enzymes to the motor neuron-specifying LIM-complex and trigger histone H3-acetylation and H3-lysine-4-trimethylation, well-established chromatin marks for active transcription. Our results suggest that Ssdps function as critical transcriptional coactivators for LIM-complexes to specify spinal neuronal identities during development.