MRC National Institute for Medical Research, London
Science for Health
Kif7 regulates mammalian Hedgehog signaling
07 July 2009
From insects to humans, the Hedgehog (Hh) signaling pathway has important roles in the development of embryos and the maintenance of adult tissues. Moreover, disruptions in this pathway are the cause of several inherited diseases and certain types of skin and brain cancer. Hh is a secreted protein and works by altering the activity of genes in responding cells. In insects this process of signalling requires a protein called Costal2, the vertebrate equivalent of this gene is Kif7. Previous studies, however, had failed to find a role for Kif7 in mammalian Hh signalling leading to the suggestion that the mechanism of Drosophila and mammalian Hh signalling had diverged. This view is challenged by the new work published in Science Signaling.
Working with C.C. Hui's group in Canada, Ana Ribeiro from James Briscoe's laboratory in NIMR's Division of Developmental Neurobiology found strong evidence that Kif7 is a critical regulator of Hh signalling. Similar to Cos2, Kif7 acts both positively and negatively in the regulation of Hh target gene expression. Nevertheless, despite their functional similarities, there appear to be mechanistic differences between Cos2 and Kif7. Together, these findings provide insight into the molecular mechanism of Hh signal transduction in vertebrate cells and reconcile the previous lack of correspondence between results from Drosophila and mammals.
This research identifies a new and important link in the Hedgehog signalling pathway that explains the discrepancy between previous studies in vertebrates and insects. It might also help explain how problems with Hh signalling can cause disease in humans.
Ana Ribeiro
Original article
The research findings are published in full in:
Helen Oi-Lam Cheung, Xiaoyun Zhang, Ana Ribeiro, Rong Mo, Shigeru Makino, Vijitha Puviindran, Kelvin K. L. Law, James Briscoe, and Chi-chung Hui (2009)
The Kinesin Protein Kif7 Is a Critical Regulator of Gli Transcription Factors in Mammalian Hedgehog Signaling
Science Signaling 2 (76), ra29. Publisher abstract
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