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Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion

Nature volume 394, pages 85–88 (1998)Cite this article

Abstract

Hedgehog (Hh) proteins act through both short-range and long-range signalling to pattern tissues during invertebrate and vertebrate development1. The mechanisms allowing Hedgehog to diffuse over a long distance and to exert its long-range effects are not understood. Here we identify a new Drosophila gene, named tout-velu, that is required for diffusion of Hedgehog. Characterization of tout-velu shows that it encodes an integral membrane protein that belongs to the EXT gene family. Members of thisfamily are involved in the human multiple exostoses syndrome, which affects bone morphogenesis2,3,4. Our results, together with the previous characterization of the role of IndianHedgehog in bone morphogenesis5,6,7, lead us to propose that themultiple exostoses syndrome is associated with abnormal diffusion of Hedgehog proteins. These results show the existence of a new conserved mechanism required for diffusion of Hedgehog.

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Figure 1: ttv affects Hh signalling.
Figure 2: ttv is required for Hh diffusion.
Figure 3: Cloning of the ttv locus.
Figure 4: Ttv is a type II integral membrane protein.

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Acknowledgements

We thank I. Guerrero, E. Hafen, B. Holmgren, P. Ingham, W. Mothes, G. Struhl and D. Raden for strains or reagents; A. Manoukian for his initial contribution to this work; W. Mothes for help with the microsome assays; B. Seed, C. Tabin and S. Goode for discussions; and S. Goode, B. Mathey-Prevot, S. van den Heuvel, M. Zeidler, E. Bach and M. Petitt for comments on the manuscript. Y.B. thanks A.Morineau for encouragement during this study. Y.B. is supported by the Boheringer Ingelheim Fonds; I.T. is supported by the Damon Runyon Fellowship. This work was supported by the NSF and the HHMI where N.P. is an investigator.

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Authors and Affiliations

  1. Department of Genetics and, 200 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Yohanns Bellaiche, Inge The & Norbert Perrimon

  2. Howard Hughes Medical Institute, Harvard Medical School, 200 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Inge The & Norbert Perrimon

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  1. Yohanns Bellaiche
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Correspondence to Norbert Perrimon.

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Bellaiche, Y., The, I. & Perrimon, N. Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion. Nature 394, 85–88 (1998). https://doi.org/10.1038/27932

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