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Sally Horne-Badovinac

Professor
shorne@uchicago.edu
Research Summary
My lab takes an integrative approach to studying organ morphogenesis. We are currently probing how cells migrate collectively & how basement membrane ECMs are assembled. Collective cell migration - The collective migration of cells within an epithelial sheet underlies tissue remodeling events associated with morphogenesis, wound repair, and the spread of many cancers. Yet little is known about how each epithelial cell coordinates its individual migratory behaviors with those of its neighbors, or how epithelial motility shapes tissues during development. We recently discovered a novel planar signaling system that coordinates leading and trailing edge dynamics between neighboring epithelial cells, and are now working to elucidate the mechanistic basis of this signaling. We are also investigating how collective cell migration can be harnesses to create a stable, planar tissue pattern within an epithelium for subsequent morphogenesis. Basement membrane dynamics – Basement membrane is a sheet-like extracellular matrix that lines the basal surface of all epithelial tissues. This complex protein network provides structural stability to the monolayer, promotes cell-cell and cell-matrix signaling, and acts as a physical barrier to metastasis. Despite their ubiquity and many essential functions, we know surprisingly little about how basement membranes are built or how they are remodeled during development. We are taking a comprehensive approach to identifying: the cellular mechanisms underlying basement membrane biosynthesis and secretion, how basement membrane biosynthetic programs are modulated to construct diverse matrix architectures, and how different basement membrane architectures ultimately influence organ morphogenesis. Experimental system – We perform these studies in the Drosophila egg chamber, which is an organ-like structure in the ovary that will give rise to one egg. Each egg chamber is comprised of a germ cell cluster, surrounded by a somatic epithelium of follicle cells. The follicle cells produce their own basement membrane, which ensheaths the organ. Though initially spherical, egg chambers lengthen as they mature. This morphogenesis depends on a dramatic collective migration of the follicle cells across their basement membrane, which causes the entire egg chamber to rotate within its surrounding matrix. Importantly, the follicle cells also remodel the basement membrane as they crawl along its surface, creating a polarized array of fibrils in the direction of tissue movement. This fibrillar matrix is then thought to act as a “molecular corset” that resists the expansive growth of the germ cells to directionally bias egg chamber growth, and thus create the elongated shape of the egg. A major strength of this system is that the collective migration and basement membrane remodeling both occur on the egg chamber’s outer surface, which allows us to image dynamic cell behaviors - in a living organ - with exquisite clarity. Moreover, we can use the sophisticated genetic tools of Drosophila to identify the underlying molecular mechanisms. Please check out the papers below to see what we have already discovered!
Keywords
Collective Cell Migration, Basement Membrane, Epithelial Morphogenesis, Membrane Trafficking, Intercellular Signaling, Drosophila
Education
  • UC Berkeley, Postdoc Cell and Developmental Biology 2008
  • UC San Francisco, PhD Biochemistry 2003
  • University of Oregon, BS Chemistry 1996
Biosciences Graduate Program Association
Awards & Honors
  • 1996 - American Foundation of Chemists Award University of Oregon
  • 1996 - Graduated summa cum laude and with Departmental Honors University of Oregon
  • 1998 - 2001 Predoctoral Fellowship National Science Foundation
  • 2001 - 2003 Predoctoral Fellowship American Heart Association
  • 2003 - 2006 Postdoctoral Fellowship Jane Coffin Childs Foundation
  • 2003 - Harold C. Weintraub Graduate Student Award Fred Hutchinson Cancer Center
  • 2009 - 2012 Young Investigator Award Edward Mallinckrodt, Jr. Foundation
  • 2010 - 2012 Basil O'Connor Starter Scholar Research Award The March of Dimes Foundation
  • 2021 - Quantrell Award for Excellence in Undergraduate Teaching The University of Chicago
Publications

  1. A Low-Tech Flow Chamber for Live Imaging of Drosophila Egg Chambers During Drug Treatments. Methods Mol Biol. 2023; 2626:277-289. View in: PubMed

  2. Optimized Fixation and Phalloidin Staining of Basally Localized F-Actin Networks in Collectively Migrating Follicle Cells. Methods Mol Biol. 2023; 2626:179-191. View in: PubMed

  3. Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration. Elife. 2022 09 26; 11. View in: PubMed

  4. Kinesin-directed secretion of basement membrane proteins to a subdomain of the basolateral surface in Drosophila epithelial cells. Curr Biol. 2022 02 28; 32(4):735-748.e10. View in: PubMed

  5. DAAM mediates the assembly of long-lived, treadmilling stress fibers in collectively migrating epithelial cells in Drosophila. Elife. 2021 11 23; 10. View in: PubMed

  6. Oriented basement membrane fibrils provide a memory for F-actin planar polarization via the Dystrophin-Dystroglycan complex during tissue elongation. Development. 2020 Jan 01. View in: PubMed

  7. In-silico definition of the Drosophila melanogaster matrisome. Matrix Biol Plus. 2019 Nov; 4:100015. View in: PubMed

  8. ESCargo: a regulatable fluorescent secretory cargo for diverse model organisms. Mol Biol Cell. 2020 12 15; 31(26):2892-2903. View in: PubMed

  9. The Drosophila micropyle as a system to study how epithelia build complex extracellular structures. Philos Trans R Soc Lond B Biol Sci. 2020 10 12; 375(1809):20190561. View in: PubMed

  10. Mobilizing the Matrix for Organ Morphogenesis. Dev Cell. 2020 07 06; 54(1):1-2. View in: PubMed

  11. Oriented basement membrane fibrils provide a memory for F-actin planar polarization via the Dystrophin-Dystroglycan complex during tissue elongation. Development. 2020 04 08; 147(7). View in: PubMed

  12. Looking deeper into tissue elongation. Nat Rev Mol Cell Biol. 2020 06; 21(6):305. View in: PubMed

  13. The dPix-Git complex is essential to coordinate epithelial morphogenesis and regulate myosin during Drosophila egg chamber development. PLoS Genet. 2019 05; 15(5):e1008083. View in: PubMed

  14. Planar-Polarized Semaphorin-5c and Plexin A Promote the Collective Migration of Epithelial Cells in Drosophila. Curr Biol. 2019 03 18; 29(6):908-920.e6. View in: PubMed

  15. Tissue Structure: A CIVICs Lesson for Adipocytes. Curr Biol. 2017 09 25; 27(18):R1013-R1015. View in: PubMed

  16. Fat-like cadherins in cell migration-leading from both the front and the back. Curr Opin Cell Biol. 2017 10; 48:26-32. View in: PubMed

  17. Fat2 and Lar Define a Basally Localized Planar Signaling System Controlling Collective Cell Migration. Dev Cell. 2017 03 13; 40(5):467-477.e5. View in: PubMed

  18. Shaping the Drosophila egg. Mol Reprod Dev. 2016 Dec; 83(12):1045. View in: PubMed

  19. Cultivation and Live Imaging of Drosophila Ovaries. Methods Mol Biol. 2016; 1478:215-226. View in: PubMed

  20. Rab10-Mediated Secretion Synergizes with Tissue Movement to Build a Polarized Basement Membrane Architecture for Organ Morphogenesis. Dev Cell. 2016 07 11; 38(1):47-60. View in: PubMed

  21. Influence of ovarian muscle contraction and oocyte growth on egg chamber elongation in Drosophila. Development. 2016 Apr 15; 143(8):1375-87. View in: PubMed

  22. Building from the Ground up: Basement Membranes in Drosophila Development. Curr Top Membr. 2015; 76:305-36. View in: PubMed

  23. Dynamic regulation of basement membrane protein levels promotes egg chamber elongation in Drosophila. Dev Biol. 2015 Oct 15; 406(2):212-21. View in: PubMed

  24. Sally Horne-Badovinac: Taking a spin around morphogenesis. J Cell Biol. 2015 Jul 06; 210(1):4-5. View in: PubMed

  25. Round and round gets you somewhere: collective cell migration and planar polarity in elongating Drosophila egg chambers. Curr Opin Genet Dev. 2015 Jun; 32:10-5. View in: PubMed

  26. Epithelial rotation promotes the global alignment of contractile actin bundles during Drosophila egg chamber elongation. Nat Commun. 2014 Nov 21; 5:5511. View in: PubMed

  27. The Drosophila egg chamber-a new spin on how tissues elongate. Integr Comp Biol. 2014 Oct; 54(4):667-76. View in: PubMed

  28. Cell-cell and cell-matrix interactions. Mol Biol Cell. 2014 Mar; 25(6):731. View in: PubMed

  29. Misshapen decreases integrin levels to promote epithelial motility and planar polarity in Drosophila. J Cell Biol. 2013 Mar 18; 200(6):721-9. View in: PubMed

  30. A Rab10-dependent mechanism for polarized basement membrane secretion during organ morphogenesis. Dev Cell. 2013 Jan 28; 24(2):159-68. View in: PubMed

  31. A screen for round egg mutants in Drosophila identifies tricornered, furry, and misshapen as regulators of egg chamber elongation. G3 (Bethesda). 2012 Mar; 2(3):371-8. View in: PubMed

  32. Developmental biology. Tubular transformations. Science. 2011 Jul 15; 333(6040):294-5. View in: PubMed

  33. Dynein regulates epithelial polarity and the apical localization of stardust A mRNA. PLoS Genet. 2008 Jan; 4(1):e8. View in: PubMed

  34. Mass transit: epithelial morphogenesis in the Drosophila egg chamber. Dev Dyn. 2005 Mar; 232(3):559-74. View in: PubMed

  35. A cellular framework for gut-looping morphogenesis in zebrafish. Science. 2003 Oct 24; 302(5645):662-5. View in: PubMed

  36. Positional cloning of heart and soul reveals multiple roles for PKC lambda in zebrafish organogenesis. Curr Biol. 2001 Oct 02; 11(19):1492-502. View in: PubMed

  37. Restricted expression of cardiac myosin genes reveals regulated aspects of heart tube assembly in zebrafish. Dev Biol. 1999 Oct 01; 214(1):23-37. View in: PubMed

  38. Vertebrate genome evolution and the zebrafish gene map. Nat Genet. 1998 Apr; 18(4):345-9. View in: PubMed

  39. Centromere-linkage analysis and consolidation of the zebrafish genetic map. Genetics. 1996 Apr; 142(4):1277-88. View in: PubMed

  40. A genetic linkage map for the zebrafish. Science. 1994 Apr 29; 264(5159):699-703. View in: PubMed

  41. Half-tetrad analysis in zebrafish: mapping the ros mutation and the centromere of linkage group I. Genetics. 1995 Apr; 139(4):1727-35. View in: PubMed
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