The ventral epidermis in the Drosophila embryo is a prime model system to uncover rules by which pattern organizers work. Epidermal pattern is etched in the cuticle laid down by epithelial cells, and across each segment the pattern appears either smooth or decorated with denticles. Denticles are specializations of a process fundamental to all epithelial cells: actin-based apical protrusions that underlie brush border microvilli, sensory bristles and stereocilia. Unique to denticles, however, each actin protrusion is intricately shaped, and this shape is choreographed reproducibly for all denticles along every line of cells of the ventral denticle field. How denticle shaping and patterning is accomplished is unknown. While our earlier focus had been largely on Hedgehog and Wingless signaling and their impact on coarse-grained pattern, our more recent work has turned to fine-grained denticle pattern which provides a high-resolution readout for the cell biology of developmental signaling. We found that Hh and Wg subdivide segments into smaller territories. By studying these territories, each of which emit key signals, we have uncovered novel interactions between the Notch and EGF- Receptor pathways (Aim 1), and found evidence that these pathways control shaping of the actin protrusions (Aim 2). In addition, the positioning of the actin protrusions in cells reflects planar cell polarity within the denticle field, and our preliminary evidence points to novel use of Myosin II for this purpose (Aim 3). Our studies may reveal novel cellular processes that link developmental signaling to morphogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM045747-17
Application #
7529194
Study Section
Development - 1 Study Section (DEV)
Program Officer
Haynes, Susan R
Project Start
1992-01-01
Project End
2010-07-31
Budget Start
2008-12-01
Budget End
2010-07-31
Support Year
17
Fiscal Year
2009
Total Cost
$279,567
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

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