The long-term focus is the control over pattern as exersized by Organizers. In the Drosophila embryo, adjacent rows of cells flanking each parasegment secrete two organizing signals, Wingless and Hedgehog. These two signals are responsible for assigning cell fates across the remainder of the parasegment, and these signals act asymmetrically from the organizing center.
The aims of this proposal focus on genes involved in Wingless signaling from the organizer. Both cell culture and transgenic approaches are outlined for arrow, which encodes a novel Wg signal transducer. The experiments will determine whether the Arrow transmembrane protein binds directly to Wingless, or complexes with the Frizzled proteins as a co-receptor. Intracellularly, yeast two-hybrid studies, as well as cell culture and in vitro analysis are proposed to explore how Arrow transduces the Wingless signal. Analogous two hybrid and in vivo studies will determine how lines, which encodes a stage-specific factor regulating the response to Wg, interacts with known or novel Wg signal transducers. Response elements in defined Wingless target genes will be studied to identify how signal integration is achieved as the organizer operates. Finally, two genetic screens are proposed to identify novel components that either interact with Arrow or Lines, or control organizer asymmetry.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM045747-12
Application #
6636026
Study Section
Genetics Study Section (GEN)
Program Officer
Greenberg, Judith H
Project Start
1992-01-01
Project End
2005-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
12
Fiscal Year
2003
Total Cost
$285,300
Indirect Cost
Name
University of Pennsylvania
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Ly, Dan; Resch, Erin; Ordiway, George et al. (2017) Asymmetrically deployed actomyosin-based contractility generates a boundary between developing leg segments in Drosophila. Dev Biol 429:165-176
Lawlor, Kynan T; Ly, Daniel C; DiNardo, Stephen (2013) Drosophila Dachsous and Fat polarize actin-based protrusions over a restricted domain of the embryonic denticle field. Dev Biol 383:285-94
Donoughe, Seth; DiNardo, Stephen (2011) dachsous and frizzled contribute separately to planar polarity in the Drosophila ventral epidermis. Development 138:2751-9
Simone, Robert P; DiNardo, Stephen (2010) Actomyosin contractility and Discs large contribute to junctional conversion in guiding cell alignment within the Drosophila embryonic epithelium. Development 137:1385-94
Dilks, Stacie A; DiNardo, Stephen (2010) Non-cell-autonomous control of denticle diversity in the Drosophila embryo. Development 137:1395-404
Baig-Lewis, Shahana; Peterson-Nedry, Wynne; Wehrli, Marcel (2007) Wingless/Wnt signal transduction requires distinct initiation and amplification steps that both depend on Arrow/LRP. Dev Biol 306:94-111
Rives, Anna F; Rochlin, Kate M; Wehrli, Marcel et al. (2006) Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing. Dev Biol 293:268-83
Walters, James W; Dilks, Stacie A; DiNardo, Stephen (2006) Planar polarization of the denticle field in the Drosophila embryo: roles for Myosin II (zipper) and fringe. Dev Biol 297:323-39
Hatini, Victor; Green, Ryan B; Lengyel, Judith A et al. (2005) The Drumstick/Lines/Bowl regulatory pathway links antagonistic Hedgehog and Wingless signaling inputs to epidermal cell differentiation. Genes Dev 19:709-18
Walters, James W; Munoz, Claudia; Paaby, Annalise B et al. (2005) Serrate-Notch signaling defines the scope of the initial denticle field by modulating EGFR activation. Dev Biol 286:415-26

Showing the most recent 10 out of 21 publications