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.
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.
|Andersen, Darcy; Horne-Badovinac, Sally (2016) Influence of ovarian muscle contraction and oocyte growth on egg chamber elongation in Drosophila. Development 143:1375-87|
|Isabella, Adam J; Horne-Badovinac, Sally (2016) Rab10-Mediated Secretion Synergizes with Tissue Movement to Build a Polarized Basement Membrane Architecture for Organ Morphogenesis. Dev Cell 38:47-60|
|Isabella, Adam J; Horne-Badovinac, Sally (2015) Dynamic regulation of basement membrane protein levels promotes egg chamber elongation in Drosophila. Dev Biol 406:212-21|
|Cetera, Maureen; Horne-Badovinac, Sally (2015) Round and round gets you somewhere: collective cell migration and planar polarity in elongating Drosophila egg chambers. Curr Opin Genet Dev 32:10-5|
|Isabella, Adam J; Horne-Badovinac, Sally (2015) Building from the Ground up: Basement Membranes in Drosophila Development. Curr Top Membr 76:305-36|
|Horne-Badovinac, Sally (2014) The Drosophila egg chamber-a new spin on how tissues elongate. Integr Comp Biol 54:667-76|
|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) Cell-cell and cell-matrix interactions. Mol Biol Cell 25:731|
|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|
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