Hedgehog signaling.

Hedgehog (Hh) proteins constitute one family of a small number of secreted signaling proteins that together regulate multiple aspects of animal development, tissue homeostasis and regeneration. Originally uncovered through genetic analyses in Drosophila, their subsequent discovery in vertebrates has provided a paradigm for the role of morphogens in positional specification. Most strikingly, the Sonic hedgehog protein was shown to mediate the activity of two classic embryonic organizing centers in vertebrates and subsequent studies have implicated it and its paralogs in a myriad of processes.

Positive and negative regulation of Gli activity by Kif7 in the zebrafish embryo.

Loss of function mutations of Kif7, the vertebrate orthologue of the Drosophila Hh pathway component Costal2, cause defects in the limbs and neural tubes of mice, attributable to ectopic expression of Hh target genes. While this implies a functional conservation of Cos2 and Kif7 between flies and vertebrates, the association of Kif7 with the primary cilium, an organelle absent from most Drosophila cells, suggests their mechanisms of action may have diverged. Here, using mutant alleles induced by Zinc Finger Nuclease-mediated targeted mutagenesis, we show that in zebrafish, Kif7 acts principally to suppress the activity of the Gli1 transcription factor.