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Edwin M. Munro

Professor
emunro@uchicago.edu
Research Summary
We study how embryos integrate biochemical signaling, cytoskeletal dynamics and cell mechanics to orchestrate complex cell and tissue behaviors. We combine live imaging, genetic perturbations, biophysical analysis, and computer simulations to address questions in three main areas: Dynamic control of self-organized actomyosin contractility, cell polarization in C. elegans, and tissue morphogenesis in aascidians The forces that shape embryonic cells and tissues are produced by dynamic contractile networks of actin filaments, myosin motors and cross-linking proteins. The big challenge is to understand how embryonic cells remodel these networks by tuning network assembly, architecture and motor activity to do a sequence of different jobs – to polarize, move, change shape and divide. To address this challenge, we combine in vivo studies in C. elegans with computer simulations, focusing on three specific examples: the long range flows that polarize cells, self assembly of the contractile ring during cytokinesis, and dynamic control of pulsatile contractions that coordinate cell shape change and rearrangements during morphogenesis. We also use C. elegans embryos as a model system to explore how cells form and stabilize polarity in response to transient polarizing cues. In recent years, we (and others) have uncovered a network of biochemical and mechanical interactions involving conserved PAR polarity proteins, small Rho family GTPases, and the acvtomyosin cytoskeleton, that do this job. We combine single molecule imaging, genetic manipulations and biophysical analysis to characterize key elements of this “mechanochemical circuit”, and to probe the fundamental design principles that allow this circuit to do it's job in such an extraordinarily robust way. Finally, we use ascidians (“sea squirts”) as a simple model system to study how embryos organize force production in space and time to shape tissues and organs. Ascidians make the many of the same structures that we do - e.g. a notochord, a simple gut and a neural tube, but they do so with very few (tens of) cells, in small optically clear embryos, that are highly accessible to genetic, pharmacological and physical manipulations. We currently focus on neural tube closure. Combining experiments with computer simulations, we ask how embryos use tissue-specific gene expression and conserved pathways for planar and apico-basal polarity to pattern actomyosin contractility in space and time to shape and close the neural tube.
Keywords
cell polarity, actomyosin contractility, morphogenesis, computational biology
Education
  • Hampshire College, Amherst, MA, BA Mathematics and Biology 05/1987
  • University of Washington, Seattle, WA, PhD Cell and Developmental Biology 01/2000
  • Fred Hutchison Cancer Research Center, Seattle, Wa, Postdoctoral fellow Cell Biology 02/2002
Biosciences Graduate Program Association
Publications

  1. Oligomerization of peripheral membrane proteins provides tunable control of cell surface polarity. Biophys J. 2022 12 06; 121(23):4543-4559. View in: PubMed

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

  3. Pulsatile contractions and pattern formation in excitable actomyosin cortex. PLoS Comput Biol. 2022 03; 18(3):e1009981. View in: PubMed

  4. Modulating RhoA effectors induces transitions to oscillatory and more wavelike RhoA dynamics in Caenorhabditis elegans zygotes. Mol Biol Cell. 2022 05 15; 33(6):ar58. View in: PubMed

  5. Filament-guided filament assembly provides structural memory of filament alignment during cytokinesis. Dev Cell. 2021 09 13; 56(17):2486-2500.e6. View in: PubMed

  6. The Dynamics of P Granule Liquid Droplets Are Regulated by the Caenorhabditis elegans Germline RNA Helicase GLH-1 via Its ATP Hydrolysis Cycle. Genetics. 2020 Jun 01; 215(2):421-434. View in: PubMed

  7. Actin bundle architecture and mechanics regulate myosin II force generation. Biophys J. 2021 05 18; 120(10):1957-1970. View in: PubMed

  8. Roadmap for the multiscale coupling of biochemical and mechanical signals during development. Phys Biol. 2021 04 14; 18(4). View in: PubMed

  9. Apical Relaxation during Mitotic Rounding Promotes Tension-Oriented Cell Division. Dev Cell. 2020 12 21; 55(6):695-706.e4. View in: PubMed

  10. The Dynamics of P Granule Liquid Droplets Are Regulated by the Caenorhabditis elegans Germline RNA Helicase GLH-1 via Its ATP Hydrolysis Cycle. Genetics. 2020 06; 215(2):421-434. View in: PubMed

  11. RhoA Mediates Epithelial Cell Shape Changes via Mechanosensitive Endocytosis. Dev Cell. 2020 01 27; 52(2):152-166.e5. View in: PubMed

  12. Differential Expression of a Classic Cadherin Directs Tissue-Level Contractile Asymmetry during Neural Tube Closure. Dev Cell. 2019 10 21; 51(2):158-172.e4. View in: PubMed

  13. Mechanosensitive Junction Remodeling Promotes Robust Epithelial Morphogenesis. Biophys J. 2019 11 05; 117(9):1739-1750. View in: PubMed

  14. Genetic induction and mechanochemical propagation of a morphogenetic wave. Nature. 2019 08; 572(7770):467-473. View in: PubMed

  15. Anillin Puts RhoA in Touch with PIP2. Dev Cell. 2019 06 17; 49(6):819-820. View in: PubMed

  16. Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo. J Cell Biol. 2018 12 03; 217(12):4230-4252. View in: PubMed

  17. Rapid diffusion-state switching underlies stable cytoplasmic gradients in the Caenorhabditis elegans zygote. Proc Natl Acad Sci U S A. 2018 09 04; 115(36):E8440-E8449. View in: PubMed

  18. Dynamic interplay of cell fate, polarity and force generation in ascidian embryos. Curr Opin Genet Dev. 2018 08; 51:67-77. View in: PubMed

  19. Filament turnover tunes both force generation and dissipation to control long-range flows in a model actomyosin cortex. PLoS Comput Biol. 2017 12; 13(12):e1005811. View in: PubMed

  20. The PAR proteins: from molecular circuits to dynamic self-stabilizing cell polarity. Development. 2017 10 01; 144(19):3405-3416. View in: PubMed

  21. Protein Clustering Shapes Polarity Protein Gradients. Dev Cell. 2017 08 21; 42(4):309-311. View in: PubMed

  22. Dynamic Opposition of Clustered Proteins Stabilizes Cortical Polarity in the C.?elegans Zygote. Dev Cell. 2015 Oct 12; 35(1):131-42. View in: PubMed

  23. A self-organized biomechanical network drives shape changes during tissue morphogenesis. Nature. 2015 Aug 20; 524(7565):351-5. View in: PubMed

  24. Isoforms Confer Characteristic Force Generation and Mechanosensation by Myosin II Filaments. Biophys J. 2015 Apr 21; 108(8):1997-2006. View in: PubMed

  25. Sequential contraction and exchange of apical junctions drives zippering and neural tube closure in a simple chordate. Dev Cell. 2015 Jan 26; 32(2):241-55. View in: PubMed

  26. Clustering of low-valence particles: structure and kinetics. Phys Rev E Stat Nonlin Soft Matter Phys. 2014 Aug; 90(2):022301. View in: PubMed

  27. Single-molecule analysis of cell surface dynamics in Caenorhabditis elegans embryos. Nat Methods. 2014 Jun; 11(6):677-82. View in: PubMed

  28. Determinants of fluidlike behavior and effective viscosity in cross-linked actin networks. Biophys J. 2014 Feb 04; 106(3):526-34. View in: PubMed

  29. Bond flexibility and low valence promote finite clusters of self-aggregating particles. Phys Rev Lett. 2012 Aug 17; 109(7):078101. View in: PubMed

  30. PAR-3 oligomerization may provide an actin-independent mechanism to maintain distinct par protein domains in the early Caenorhabditis elegans embryo. Biophys J. 2011 Sep 21; 101(6):1412-22. View in: PubMed

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

  32. Force generation, transmission, and integration during cell and tissue morphogenesis. Annu Rev Cell Dev Biol. 2011; 27:157-84. View in: PubMed

  33. Quantitative variation in autocrine signaling and pathway crosstalk in the Caenorhabditis vulval network. Curr Biol. 2011 Apr 12; 21(7):527-38. View in: PubMed

  34. Sequential activation of apical and basolateral contractility drives ascidian endoderm invagination. Curr Biol. 2010 Sep 14; 20(17):1499-510. View in: PubMed

  35. Cellular symmetry breaking during Caenorhabditis elegans development. Cold Spring Harb Perspect Biol. 2009 Oct; 1(4):a003400. View in: PubMed

  36. Pushing the frontiers of development. Development. 2009 Jan; 136(2):173-7. View in: PubMed

  37. FGF3 in the floor plate directs notochord convergent extension in the Ciona tadpole. Development. 2009 Jan; 136(1):23-8. View in: PubMed

  38. Processing bodies and germ granules are distinct RNA granules that interact in C. elegans embryos. Dev Biol. 2008 Nov 01; 323(1):76-87. View in: PubMed

  39. Cytokinetic furrowing in toroidal, binucleate and anucleate cells in C. elegans embryos. J Cell Sci. 2008 Feb 01; 121(Pt 3):306-16. View in: PubMed

  40. Asymmetric cell division: a CAB driver for spindle movements. Curr Biol. 2007 Aug 21; 17(16):R639-41. View in: PubMed

  41. Astral signals spatially bias cortical myosin recruitment to break symmetry and promote cytokinesis. Curr Biol. 2007 Aug 07; 17(15):1286-97. View in: PubMed

  42. The microtubules dance and the spindle poles swing. Cell. 2007 May 04; 129(3):457-8. View in: PubMed

  43. Cellular morphogenesis in ascidians: how to shape a simple tadpole. Curr Opin Genet Dev. 2006 Aug; 16(4):399-405. View in: PubMed

  44. Conditional dominant mutations in the Caenorhabditis elegans gene act-2 identify cytoplasmic and muscle roles for a redundant actin isoform. Mol Biol Cell. 2006 Mar; 17(3):1051-64. View in: PubMed

  45. PAR proteins and the cytoskeleton: a marriage of equals. Curr Opin Cell Biol. 2006 Feb; 18(1):86-94. View in: PubMed

  46. Ascidian prickle regulates both mediolateral and anterior-posterior cell polarity of notochord cells. Curr Biol. 2005 Jan 11; 15(1):79-85. View in: PubMed

  47. Cortical flows powered by asymmetrical contraction transport PAR proteins to establish and maintain anterior-posterior polarity in the early C. elegans embryo. Dev Cell. 2004 Sep; 7(3):413-24. View in: PubMed

  48. C. elegans PAR-3 and PAR-6 are required for apicobasal asymmetries associated with cell adhesion and gastrulation. Development. 2003 Nov; 130(22):5339-50. View in: PubMed

  49. Ingeneue: a versatile tool for reconstituting genetic networks, with examples from the segment polarity network. J Exp Zool. 2002 Oct 15; 294(3):216-51. View in: PubMed

  50. Robustness, flexibility, and the role of lateral inhibition in the neurogenic network. Curr Biol. 2002 May 14; 12(10):778-86. View in: PubMed

  51. Polarized basolateral cell motility underlies invagination and convergent extension of the ascidian notochord. Development. 2002 Jan; 129(1):13-24. View in: PubMed

  52. Morphogenetic pattern formation during ascidian notochord formation is regulative and highly robust. Development. 2002 Jan; 129(1):1-12. View in: PubMed

  53. The segment polarity network is a robust developmental module. Nature. 2000 Jul 13; 406(6792):188-92. View in: PubMed

  54. Modularity in animal development and evolution: elements of a conceptual framework for EvoDevo. J Exp Zool. 1999 Dec 15; 285(4):307-25. View in: PubMed
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