In the vertebrate spinal cord, the LIM-homeodomain transcription factors Isl1 and Lhx3 act in concert with the linker protein NLI to regulate neuronal differentiation: Lhx3/NLI complexes promote V2a interneuron fate, whereas Lhx3/Isl1/NLI complexes direct motor neuron differentiation. However, how these complexes mediate transcriptional activation is still poorly understood. Soo-Kyung Lee and co-workers now (p. ) elucidate a role for the single-stranded DNA binding proteins Ssdp1/2 in this process. Ssdps are known to interact with NLI in various contexts and have been implicated as possible components of LIM-containing complexes. Here, the authors show that Ssdp1/2 interact with Lhx3, Isl1 and NLI, and that they are required for efficient activation of target genes – both in vivo and in vitro. In both chick and mouse, Ssdp1/2 knockdown compromises V2a and motor neuron differentiation. Mechanistically, Ssdp1/2 appear to be involved in recruiting histone-modifying enzymes to Lhx3/Isl1 targets, triggering deposition of active chromatin marks. Thus, this work identifies Ssdps as key components of transcriptional regulator complexes in the spinal cord and it is likely that they play similar roles in other developmental contexts.
