Research ArticleDevelopmental Biology

The Kinesin Protein Kif7 Is a Critical Regulator of Gli Transcription Factors in Mammalian Hedgehog Signaling

Science Signaling  23 Jun 2009:
Vol. 2, Issue 76, pp. ra29
DOI: 10.1126/scisignal.2000405

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A Mammalian Cos2 Homolog

Hedgehog (Hh) signaling is an evolutionarily conserved pathway required for tissue patterning and cell fate determination during development. In the absence of Hh, the Drosophila kinesin-like protein Costal2 (Cos2) mediates the proteolytic processing of the transcription factor Cubitus interruptus (Ci) into a repressor of gene transcription. However, in the presence of Hh, Cos2 interacts with the transmembrane protein Smoothened (Smo) and the repressor form of Ci is not produced. Cheung et al. now provide several lines of evidence suggesting that Kif7 functions in a similar capacity to Cos2 in mammalian Hh signaling. As would be expected for a Cos2 homolog, Kif7 interacted with mammalian Gli transcription factors (the mammalian homologs of Ci) and inhibited the activity of Gli2. In addition, genetic ablation of Kif7 in mice altered the abundance of activator and repressor forms of Gli transcription factors and produced skeletal defects reminiscent of those seen in Gli3-deficient mice. Furthermore, genetic analysis revealed that Kif7 functions downstream of Smo to exert positive and negative effects on Hh patterning of the ventral neural tube. These results suggest that Hedgehog signaling in Drosophila and vertebrates is more mechanistically similar than previously suspected.