Signaling Activities of the Drosophila wingless Gene Are Separately Mutable and Appear to be Transduced at the Cell Surface

INVESTIGATIONS

Signaling Activities of the Drosophila wingless Gene Are Separately Mutable and Appear to be Transduced at the Cell Surface

A. Bejsovec and E. Wieschaus
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544

The Drosophila segment polarity gene wingless encodes an intercellular signaling molecule that transmits positional information during development of the embryonic epidermis. We have explored the mechanism of wg signal transduction by perturbing cellular processes genetically and by performing structure/function analysis of the Wg protein. We present evidence that Wingless protein may transduce signal at the cell surface and that Wg may bind to its cell surface receptor without necessarily activating it. We demonstrate that two specific signaling activities of the Wg molecule can be disrupted independently by mutation. Sequence analysis indicates that these different signaling activities are not promoted by discrete functional domains, but rather that the overall conformation of the molecule may control distinct signaling functions. We conclude that wg signaling may involve complex interactions between the Wg ligand and its cell surface receptor molecule(s) and that some of this complexity resides within the Wg ligand itself.

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				J. D. Axelrod, J. R. Miller, J. M. Shulman, R. T. Moon, and N. Perrimon Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways Genes & Dev., August 15, 1998; 12(16): 2610 - 2622. [Abstract] [Full Text]

				H. Dierick and A Bejsovec Functional analysis of Wingless reveals a link between intercellular ligand transport and dorsal-cell-specific signaling Development, January 12, 1998; 125(23): 4729 - 4738. [Abstract] [PDF]

				K. M. Cadigan and R. Nusse Wnt signaling: a common theme in animal development Genes & Dev., December 15, 1997; 11(24): 3286 - 3305. [Full Text] [PDF]

				L O'Keefe, S. Dougan, L Gabay, E Raz, B. Shilo, and S DiNardo Spitz and Wingless, emanating from distinct borders, cooperate to establish cell fate across the Engrailed domain in the Drosophila epidermis Development, January 12, 1997; 124(23): 4837 - 4845. [Abstract] [PDF]

				R Hays, G. Gibori, and A Bejsovec Wingless signaling generates pattern through two distinct mechanisms Development, January 10, 1997; 124(19): 3727 - 3736. [Abstract] [PDF]

				T. Haerry, T. Heslip, J. Marsh, and M. O'Connor Defects in glucuronate biosynthesis disrupt Wingless signaling in Drosophila Development, January 8, 1997; 124(16): 3055 - 3064. [Abstract] [PDF]

				D. Jackson and D. I. H. Linzer Proliferin Transport and Binding in the Mouse Fetus Endocrinology, January 1, 1997; 138(1): 149 - 155. [Abstract] [Full Text] [PDF]

				S Hoppler, J D Brown, and R T Moon Expression of a dominant-negative Wnt blocks induction of MyoD in Xenopus embryos. Genes & Dev., November 1, 1996; 10(21): 2805 - 2817. [Abstract] [PDF]

				K. Cadigan and R Nusse wingless signaling in the Drosophila eye and embryonic epidermis Development, January 9, 1996; 122(9): 2801 - 2812. [Abstract] [PDF]