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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.
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11091085
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Fig. 2. Normal and Gli2-induced HKI expression. In situ hybridizations with an HKI probe (A–D,G–I) and a neural-specific N-Tubulin (N-tub) probe (E,F) were performed on stage ˜12.5 (A,D), ˜15 (B,C,E,F) and ˜28 (G–I) embryos. (A–C,E–I) are uninjected embryos and (D) was injected with Gli2 RNA into one blastomere at the two-cell stage, resulting in unilateral expression of myc-tagged Gli2 protein (brown staining labeled ‘myc’). (A,B,D,E) anterior is to the top or top-left and the dorsal side is facing up. (G) anterior is to the left and the dorsal side is to the top. (C,F,H,I) Cross-sections of embryos; the dorsal side is to the top. Abbreviations: cg, cranial ganglia; e, eye; h, heart; i, interneurons; nc, notochord; nm, cells that may be neuromasts; nt, neural tube; m, motorneurons; s, sensory neurons; so, somites; tg, trigeminal ganglia. Dashed lines indicate the axes of symmetry. Solid black lines and letters in parenthesis next to them in (G) indicate the approximate level corresponding to the sections shown in panels (H,I). Arrows in (D) point to ectopic expression of HKI (blue), in (G) arrows point to cranial ganglia, and in (H,I) arrows point to ventral neurons, possibly motorneurons.
