Little is known about the downstream genes regulated by Gli zinc finger transcription factors, which are targets and mediators of Hedgehog signaling. Specifically, the identity and regulation of genes which mediate Gli2 function in neurogenesis are unclear. We describe here the cloning of frog Hexokinase I (HKI) as a Gli2-responsive gene. We show that HKI expression is induced by Gli2 and that it is detected in defined neuronal populations. Since the primary energy source of the brain is derived from glucose metabolism and hexokinase catalyses the first and rate limiting step in this process, the conversion of glucose into glucose-6-phosphate, these findings suggest a link between the regulation of neuronal induction and differentiation.