, 2008). It is conceivable

that in zebrafish recently reported differences in outward K+ currents between two embryonic motoneurons, dorsal MiP and ventral CaP ( Moreno and Ribera, 2009), may be regulated by the differential expression of Islet1/2 in these neurons ( Appel et al., 1995). We provide substantial evidence that differential expression of islet in vMNs versus dMNs is critical for determining subtype-specific differences in Sh-mediated K+ currents. Because these selleck kinase inhibitor Sh-mediated K+ currents regulate action potential frequency, they will contribute to network function. Comparable to our findings in Drosophila, in both the mouse cochlea and cortex, neurons that fire only a small number of action potentials to a given current pulse (termed rapidly adapting) express a DTx-sensitive Kv1 (Sh-like) K+ current. By contrast, neurons that fire many action potentials (slowly adapting) do not. The firing pattern of rapidly adapting neurons can be transformed into that of slowly adapting neurons by application of the Sh-specific blocker DTx ( Miller et al., 2008). Our own data are consistent with such a role for Sh because we show that dMNs which express Sh, fire fewer action potentials than vMNs. Moreover, the number of action potentials fired by dMNs is increased by genetic or pharmacological block of the Sh-mediated AZD2281 order K+ current. We envisage, therefore, that regulation of action potential firing, through Islet-mediated transcriptional

control of a Sh-like K+ current, might be well conserved. While the presence of early factors able to regulate ion-channel gene expression is predictive of predetermination of electrical signaling properties in embryonic neurons, a challenge remains to understand how individual neurons decode this information. In the Drosophila ventral nerve cord, we find that the presence or absence of a Sh-mediated K+ current is determined by whether islet is expressed or not. Thus, Islet

seems to act as a binary switch; when present it prevents expression of Sh and vice versa. However, it seems unlikely Phosphatidylinositol diacylglycerol-lyase that all combinatorial factors act in this way. For example, the activity of Eve seems to be related to its relative level of expression, since endogenous Eve only partially represses transcription of slowpoke (a Ca2+-dependent K+ channel) in the dorsal motoneuron aCC ( Pym et al., 2006). It remains to be determined whether efficacy of regulatory activity is specific to individual transcription factors or to target genes. We show here that the Lim-homeodomain transcription factor Islet forms part of an intrinsic “decision-making” process that is critical to specifying subtype-specific electrical properties in developing motoneurons. It might be argued that input from pre- and postsynaptic partners is involved in setting early electrophysiological differences between neurons. Indeed such inputs play a pivotal role during axonogenesis and synapse development.