Our long-term goal is to understand the genetic control of morphogenesis at the interface between the cellular and tissue levels. We use planar polarity in the Drosophila wing as a model system. A similar planar polarity is involved in the convergent extension movements of vertebrate gastrulation and for the function of a number of adult epithelia. For example, the epithelial cells that line our respiratory tract have apical cilia that beat in a polarized manner. The Drosophila wing contains about 30,000 cells, each of which produces a single distally pointing cuticular hair. Our genetic analysis showed that the frizzled signaling/signal transduction pathway regulates hair polarity by controlling the subcellular location for hair morphogenesis. The frizzled pathway has both cell autonomous and cell non-autonomous components. An early step in the cell autonomous pathway is the accumulation of several proteins including Frizzled along the distal edge of the cell. This leads to the cytoskeleton being activated so that a hair forms at the distal most part of the cell. The function of the Inturned and Fuzzy proteins is required to couple the distal accumulation of Fz to the cytoskeleton. Our hypothesis is that Inturned and Fuzzy serve as adapter proteins. We will test this by identifying proteins that interact with Inturned and Fuzzy. Mutations in the recently cloned fritz gene produce wing phenotypes that are indistinguishable from inturned and fuzzy. We will continue the molecular genetic analysis of fritz and determine if this protein is part of a complex with Inturned and Fuzzy. We will use time-lapse confocal microscopy to examine the kinetics of accumulation of proteins at the distal edge of wing cells and if this is altered in mutants. During the past period of support, we identified a transcription factor encoding gene where mutations give rise to a polarity phenotype. Genetic strategies will be used to determine if this gene is a downstream component of the frizzled pathway. Mutations in several genes that encode cadhenn domain containing proteins give rise to planar polarity phenotypes. For one of these genes we will determine the relative importance of adhesion versus signal transduction for the mutant phenotype.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM037163-19
Application #
6754398
Study Section
Genetics Study Section (GEN)
Program Officer
Haynes, Susan R
Project Start
1986-07-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
19
Fiscal Year
2004
Total Cost
$330,456
Indirect Cost
Name
University of Virginia
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Wang, Ying; Naturale, Victor F; Adler, Paul N (2017) Planar Cell Polarity Effector Fritz Interacts with Dishevelled and Has Multiple Functions in Regulating PCP. G3 (Bethesda) 7:1323-1337
Sobala, Lukasz F; Adler, Paul N (2016) The Gene Expression Program for the Formation of Wing Cuticle in Drosophila. PLoS Genet 12:e1006100
Lu, Qiuheng; Adler, Paul N (2015) The diaphanous gene of Drosophila interacts antagonistically with multiple wing hairs and plays a key role in wing hair morphogenesis. PLoS One 10:e0115623
Sobala, Lukasz F; Wang, Ying; Adler, Paul N (2015) ChtVis-Tomato, a genetic reporter for in vivo visualization of chitin deposition in Drosophila. Development 142:3974-81
Lu, Qiuheng; Schafer, Dorothy A; Adler, Paul N (2015) The Drosophila planar polarity gene multiple wing hairs directly regulates the actin cytoskeleton. Development 142:2478-86
Wang, Ying; Yan, Jie; Lee, Haeryun et al. (2014) The proteins encoded by the Drosophila Planar Polarity Effector genes inturned, fuzzy and fritz interact physically and can re-pattern the accumulation of ""upstream"" Planar Cell Polarity proteins. Dev Biol 394:156-69
Fagan, Jeremy K; Dollar, Gretchen; Lu, Qiuheng et al. (2014) Combover/CG10732, a novel PCP effector for Drosophila wing hair formation. PLoS One 9:e107311
Adler, Paul N; Sobala, Lukasz F; Thom, Desean et al. (2013) dusky-like is required to maintain the integrity and planar cell polarity of hairs during the development of the Drosophila wing. Dev Biol 379:76-91
Adler, Paul N (2012) The frizzled/stan pathway and planar cell polarity in the Drosophila wing. Curr Top Dev Biol 101:1-31
Nagaraj, Ranganayaki; Adler, Paul N (2012) Dusky-like functions as a Rab11 effector for the deposition of cuticle during Drosophila bristle development. Development 139:906-16

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