To determine the expression pattern of disp, wild-type embryos and pupal imaginal discs were probed with anti-sense DISP RNA. Ubiquitous disp expression is observed throughout the embryo and imaginal discs. Thus, based on its expression pattern, disp is neither a transcriptional target nor a spatial determinant of Hh signaling (Burke, 1999).
To determine if disp is required specifically for either the Hh or Wg pathway, large disp minus clones were generated in the adult wing, a tissue in which the two pathways function independently of one another in distinct subpopulations of cells. Hh plays a role in the functioning of the anterior-posterior boundary in the wing, while Wg functions at the wing margin. A reduction in Hh activity causes a strong narrowing of the intervein region between longitudinal veins L3 and L4, a reflection of Hh's role at the anterior-posterior boundary, while loss of Wg signaling in the wing primordium results in loss of wing margin. Although disp minus clones can encompass large regions of Wg-sending and Wg-receiving cells, such clones contribute to wild-type wing margin structures, which indicates that disp function is not required for the Wg signaling pathway. However, when located in the posterior compartment, large clones cause a significant reduction in the distance between veins L3 and L4, a phenotype typical for the reduction of Hh signaling at the A/P boundary. Thus, it is concluded that disp is acting in the Hh signaling pathway (Burke, 1999).
Bellaiche, Y., The, I. and Perrimon, N. (1998). Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion. Nature 394: 85-88.
Burke, R., et al. (1999). Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified hedgehog from signaling cells. Cell 99(7): 803-15.
Carstea, E. D., et al. (1997). Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis. Science 277(5323): 228-31.
Caspary, T., et al. (2002). Mouse Dispatched homolog1 is required for long-range, but not juxtacrine, Hh signaling. Curr. Biol. 12: 1628-1632. 12372258
Kawakami, T., et al. (2002). Mouse dispatched mutants fail to distribute hedgehog proteins and are defective in hedgehog signaling. Development 129: 5753-5765. 12421714
Lee, J. J., Ekker, S. C., von Kessler, D. P., Porter, J. A., Sun, B. I. and Beachy, P. A. (1994). Autoproteolysis in hedgehog protein biogenesis. Science 266, 1528-1537.
Loftus, S. K., et al. (1997). Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene. Science 277(5323): 232-5.
Ma, Y., et al. (2002). Hedgehog-mediated patterning of the mammalian embryo requires transporter-like function of Dispatched. Cell 111: 63-75. 12372301
Michaux, G., Gansmuller, A., Hindelang, C. and Labouesse, M. (2000). CHE-14, a protein with a sterol-sensing domain, is required for apical sorting in C. elegans ectodermal epithelial cells. Curr. Biol. 10: 1098-1107. 10996790
Neufeld, E. B., et al. (1999). The Niemann-Pick C1 protein resides in a vesicular compartment linked to retrograde transport of multiple lysosomal cargo. J. Biol. Chem. 274(14): 9627-35.
Perens, E. A. and Shaham, S. (2005). C. elegans daf-6 encodes a patched-related protein required for lumen formation. Dev. Cell 8(6):893-906. 15935778
Porter, J. A., von Kessler, D. P., Ekker, S. C., Young, K. E., Lee, J. J., Moses, K. and Beachy, P. A. (1995). The product of hedgehog autoproteolytic cleavage active in local and long-range signaling. Nature 374: 363-366.
Porter, J. A., et al. (1996a). Hedgehog patterning activity: role of a lipophilic modification mediated by the carboxy-terminal autoprocessing domain. Cell 86: 21-34.
Porter, J. A., Young, K. E. and Beachy, P. A. (1996b). Cholesterol modification of hedgehog signaling proteins in animal development. Science 274: 255-259.
Tian, H., Tenzen, T. and McMahon, A. P. (2004). Dose dependency of Disp1 and genetic interaction between Disp1 and other hedgehog signaling components in the mouse. Development 131: 4021-4033. 15269168
Tian, H., et al. (2005). Mouse Disp1 is required in sonic hedgehog-expressing cells for paracrine activity of the cholesterol-modified ligand. Development 132: 133-142. 15576405
Zeng, X., et al. (2001), A freely diffusible form of Sonic hedgehog mediates long-range signalling. Nature 411: 716-720. 11395778
date revised: 30 August 2005
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