During nervous system development, a multitude of different neuronal cell types are generated in a process partly regulated through the combinatorial expression of LIM homeodomain transcription factors. Now, on , Song, Pfaff and co-workers investigate the effects of changing the concentrations of the LIM homeodomain proteins Islet1 and Islet2, and of the putative Islet protein antagonist Lmo4, on the differentiation of motor neurons (MNs) and of V2a interneurons in mice. By combining different mutations that affect Islet expression, the authors demonstrate that reducing Islet protein levels leads to increased V2a interneuron differentiation at the expense of MN formation. Unexpectedly, depleting Lmo4 levels alone has no effect on MN or V2a interneuron specification; however, the loss of MNs caused by Islet protein depletion is rescued in mice that lack Lmo4. These findings indicate that both Islet protein and Lmo4 levels contribute to the make-up of LIM complexes in vivo, and the authors speculate that Lmo4 might facilitate fate decisions when LIM protein concentrations are low.
