Regulatory interactions between patterning genes and proneural genes are believed to coordinate the genetic programmes that regionalize the developing spinal cord and brain. Such an interaction, between Pax6 and the proneural gene Ngn2, is now shown to exist on by Scardigli et al. In developing mouse spinal cord and brain, the activity of the Ngn2enhancer E1 is highest where Pax6 is most highly expressed. This enhancer contains a low-affinity binding site for Pax6, and its activity is disrupted in Pax6 null mice and in mice carrying mutated binding site sequences. Thus Pax6 is required for the activation of E1. However, this only occurs in vivo, as the authors show, at high Pax6 concentrations –increasing Pax6 dosage in mouse embryos, for example, extends the domains of E1 activity. Together, these comprehensive findings highlight how Pax6 expression gradients might establish specific gene-expression domains in the CNS and brain.
