QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hatini, V. Articles by DiNardo, S. Search for Related Content PubMed PubMed Citation Articles by Hatini, V. Articles by DiNardo, S. Social Bookmarking                   What's this?

RESEARCH PAPER

The Drumstick/Lines/Bowl regulatory pathway links antagonistic Hedgehog and Wingless signaling inputs to epidermal cell differentiation

¹ Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA; ² Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California 90095, USA; ³ Department of Anatomy, University of Cambridge, Cambridge, CB2 3DY, United Kingdom

Hedgehog and Wingless signaling in the Drosophila embryonic epidermis represents one paradigm for organizer function. In patterning this epidermis, Hedgehog and Wingless act asymmetrically, and consequently otherwise equivalent cells on either side of the organizer follow distinct developmental fates. To better understand the downstream mechanisms involved, we have investigated mutations that disrupt dorsal epidermal pattern. We have previously demonstrated that the gene lines contributes to this process. Here we show that the Lines protein interacts functionally with the zinc-finger proteins Drumstick (Drm) and Bowl. Competitive protein-protein interactions between Lines and Bowl and between Drm and Lines regulate the steady-state accumulation of Bowl, the downstream effector of this pathway. Lines binds directly to Bowl and decreases Bowl abundance. Conversely, Drm allows Bowl accumulation in drm-expressing cells by inhibiting Lines. This is accomplished both by outcompeting Bowl in binding to Lines and by redistributing Lines to the cytoplasm, thereby segregating Lines away from nuclearly localized Bowl. Hedgehog and Wingless affect these functional interactions by regulating drm expression. Hedgehog promotes Bowl protein accumulation by promoting drm expression, while Wingless inhibits Bowl accumulation by repressing drm expression anterior to the source of Hedgehog production. Thus, Drm, Lines, and Bowl are components of a molecular regulatory pathway that links antagonistic and asymmetric Hedgehog and Wingless signaling inputs to epidermal cell differentiation. Finally, we show that Drm and Lines also regulate Bowl accumulation and consequent patterning in the epithelia of the foregut, hindgut, and imaginal discs. Thus, in all these developmental contexts, including the embryonic epidermis, the novel molecular regulatory pathway defined here is deployed in order to elaborate pattern across a field of cells.

[Keywords: Patterning; Hedgehog; Wingless; Drumstick; Lines; Bowl]

Received September 30, 2004; revised version accepted January 24, 2005.

⁴ Present address: Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA 02111, USA.

⁵ Corresponding author.
E-MAIL victor.hatini{at}tufts.edu; FAX (617) 636-3676.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Nusinow, L. Greenberg, and V. Hatini Reciprocal roles for bowl and lines in specifying the peripodial epithelium and the disc proper of the Drosophila wing primordium Development, September 15, 2008; 135(18): 3031 - 3041. [Abstract] [Full Text] [PDF]

				S. Vincent, N. Perrimon, and J. D. Axelrod Hedgehog and Wingless stabilize but do not induce cell fate during Drosophila dorsal embryonic epidermal patterning Development, August 15, 2008; 135(16): 2767 - 2775. [Abstract] [Full Text] [PDF]

				C. Bras-Pereira, J. Bessa, and F. Casares Odd-skipped genes specify the signaling center that triggers retinogenesis in Drosophila Development, November 1, 2006; 133(21): 4145 - 4149. [Abstract] [Full Text] [PDF]

				R. E. Goldstein, O. Cook, T. Dinur, A. Pisante, U. C. Karandikar, A. Bidwai, and Z. Paroush An eh1-Like Motif in Odd-skipped Mediates Recruitment of Groucho and Repression In Vivo Mol. Cell. Biol., December 15, 2005; 25(24): 10711 - 10720. [Abstract] [Full Text] [PDF]