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Developmental biology

Boning up on Hedgehog's movements

Nature volume 394, pages 16–17 (1998)Cite this article

Members of the Hedgehog (Hh) family of secreted proteins are known to act as intercellular signals in a multitude of processes, ranging from neuronal specification to bone morphogenesis1. In the fruitfly Drosophila melanogaster, six genes have so far been implicated in transduction of the Hh signal, and the human homologues of three of these have been identified as oncogenes or tumour suppressors in the skin and nervous system1. On page 85 of this issue, Bellaiche et al.2 report that they have discovered a seventh gene that is involved in Hh signalling in Drosophila. The authors call this gene tout-velu (ttv) — a reference, in French, to the mutants' ‘hairy’ appearance — and show that it mediates movement of the Hh protein across responding cells in the Drosophila wing. A twist to the story is that ttv is homologous to EXT-1 and EXT-2 — two genes that are associated with benign bone tumours (exostoses) in humans3,4. These findings raise intriguing questions about the mechanism of Hh signalling, while shedding new light on the pathogenesis of human multiple exostoses syndrome.

The ttv gene was originally identified through its hh-like embryonic phenotype7, so, in principle, it could have acted at any point in the Hh signalling pathway. Crucially, however, Bellaiche et al. discovered that the activation of Hh-target genes is not abolished in the absence of ttv; rather, such activation becomes restricted to cells immediately adjacent to those secreting the protein. This gave a hint that it may be diffusion of Hh, rather than Hh signalling per se, that is disrupted in ttv mutants. To explore this possibility, the authors made genetically mosaic animals in which large clones of cells lack expression of both ttv and ptc. When such cells abutted Hh-secreting cells, the result was striking — instead of passing freely across the cells, as it would in the absence of Ptc alone, the Hh protein travelled no further than the first cell that it encountered.

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Figure 1: Diffusion of the Hedgehog (Hh) protein in Drosophila is regulated by the Patched (Ptc) and Tout-velu (Ttv) proteins.

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  1. the Developmental Genetics Programme, The Krebs Institute, University of Sheffield, Firth Court, S10 2TN, Sheffield, UK

    Philip W. Ingham

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Ingham, P. Boning up on Hedgehog's movements. Nature 394, 16–17 (1998). https://doi.org/10.1038/27764

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