The long term goal of this research is to determine how the dynamic regulation of cell shape, polarity and adhesion across cell populations sculpts an organ's shape during development. To this end, we are using genetic and cell biological approaches in Drosophila to investigate how a novel form of planar polarity within the follicle cell epithelium creates the elongated shape of a simple organ-like unit known as an egg chamber. Planar polarity is a developmental mechanism in which individual cells are coordinately polarized within the plane of a tissue to provide directional information for subsequent morphogenetic events. Pioneering work on this phenomenon in the fly wing and eye led to the discovery of the Frizzled planar cell polarity pathway, which is now known to shape the vertebrate body axis, inner ear, kidneys and neural tube. The Frizzled signaling cassette plays no role in egg chamber elongation, however, indicating that the investigation of this process is likely to define a new and perhaps similarly conserved molecular framework regulating planar polarity and organ shape. Our first two specific aims are designed to elucidate the cellular mechanisms that underlie this unconventional planar polarity system.
Aim 1 will use genetic manipulations to test the hypothesis that a specialized cell type known as the polar cells induces planar polarity in the neighboring follicle cells, while Aim 2 will use fixed and live imaging techniques to explore the development and function of a polarized cell protrusive activity that represents the most dramatic morphological readout of planar polarity in this tissue. To complement these cellular analyses, we performed a pilot genetic screen that identified a key molecular pathway regulating planar patterning and morphogenesis in this epithelium.
Aim 3 will use genetic and biochemical approaches to investigate the function of this signaling cascade, and Aim 4 will employ a highly efficient screening strategy to extend the search for novel egg shape regulators to other regions of the Drosophila genome. Together these studies will reveal the cellular and molecular mechanisms controlling follicle cell planar polarity and egg chamber elongation, and are likely to reveal general principles guiding organ morphogenesis in wide range of systems.

Public Health Relevance

The proper function of vital organs requires that they attain their proper shapes during embryonic development. When these processes go awry, birth defects metabolic diseases result. The goal of this research is to use the experimental tractability of fruit flies to reveal novel cellular and molecular mechanisms guiding organ morphogenesis.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01GM094276-05
Application #
8691894
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Hoodbhoy, Tanya
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Chicago
Department
Genetics
Type
Schools of Medicine
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60637
Cetera, Maureen; Ramirez-San Juan, Guillermina R; Oakes, Patrick W et al. (2014) Epithelial rotation promotes the global alignment of contractile actin bundles during Drosophila egg chamber elongation. Nat Commun 5:5511
Horne-Badovinac, Sally (2014) The Drosophila egg chamber-a new spin on how tissues elongate. Integr Comp Biol 54:667-76
Lerner, David W; McCoy, Darcy; Isabella, Adam J et al. (2013) A Rab10-dependent mechanism for polarized basement membrane secretion during organ morphogenesis. Dev Cell 24:159-68
Lewellyn, Lindsay; Cetera, Maureen; Horne-Badovinac, Sally (2013) Misshapen decreases integrin levels to promote epithelial motility and planar polarity in Drosophila. J Cell Biol 200:721-9
Horne-Badovinac, Sally; Hill, Joseph; Gerlach 2nd, Gary et al. (2012) A screen for round egg mutants in Drosophila identifies tricornered, furry, and misshapen as regulators of egg chamber elongation. G3 (Bethesda) 2:371-8