Medaka spalt acts as a target gene of hedgehog signaling

In vertebrates, pattern formation in the eye, central nervous system, somites, and limb depends on hedgehog activity, but a general target gene controlled by hedgehog in all these signaling centers has remained largely elusive. The medaka fish gene spalt encodes a zinc-finger transcription factor, which is expressed in all known hedgehog signaling centers of the embryo and in the organizer region at the midbrain-hindbrain boundary. We show that the spalt expression domains expand in response to ectopic hedgehog activity and narrow in the presence of protein kinase A activity, an antagonist of hedgehog signaling, indicating that spalt is a hedgehog target gene. Our results also suggest a signaling mechanism for anterior-posterior patterning of the vertebrate brain that controls spalt expression at the midbrain-hindbrain boundary in a protein kinase A dependent manner likely to involve an unknown member of the hedgehog family.