Education

B.A. Mathematics and Biology, Hampshire College (1987)
PhD Zoology, University of Washington (2000)

BPHYS Students

William McFadden, PhD

Elizabeth White

Research Summary

My lab seeks to understand how the dynamic behaviors of embryonic cells and tissues emerge through the interplay between biochemical regulation, cytoskeletal dynamics and cytomechanics. We are particularly interested in how embryonic cells organize, modulate and deploy actomyosin contractility do different jobs in different contexts. We focus in two main areas: cell polarization and asymmetric cell division in the nematode worm C. elegans, and the dynamics of cellular morphogenesis in ascidians. We work at the interface between experimental and computational biology, combining quantitative microscopy, molecular genetic, pharmacological and physical manipulations, and detailed computer simulations that predict cell and tissue level dynamics from known or hypothesized molecular interactions

Dynamics of cell polarization in C. elegans.
We are using C. elegans as model system to explore how conserved interactions among PAR proteins, small GTPases, and the actomyosin cytoskeleton orchestrate the establishment and maintenance of cellular asymmetries in response to a transient polarizing cue. In previous work, we and others have identified a system of intertwined mechanical and biochemical interactions in which: (i) actomyosin contractility powers cortical flows that (ii) redistribute Par proteins and the small GTPases Rho and Cdc-42, which in turn (iii) cross-regulate one another and modulate actomyosin to influence their own redistribution. Working back and forth between experiments ad computer simulations, we seek to identify and characterize the key elements of this feedback system, and to understand the fundamental design principles that allow this system to do it's job in such an extraordinarily robust way. Because all of the key elements of this system are highly conserved, these studies should deeply inform our understanding of polarization in many other contexts.

Dynamics of cellular morphogenesis in ascidians.
We are also using the "simple" ascidian to probe the mechanisms that govern tissue morphogenesis. Ascidians perform all of the classical morphogenetic movements of metazoan development - invagination, convergent extension, epiboly, etc - but with few (tens of) cells in small optically clear embryos that are highly accessible to genetic, pharmacological and physical manipulations. We focus on two central elements of chordate morphogenesis - notochord formation and neurulation. Combining experiments with detailed computer simulations, we address two general questions: How do cells exploit conserved pathways for planar and apico-basal polarity to organize the machinery that governs local contractility, motility and cell-cell adhesion? How are the local actions of this machinery integrated across many cells to produce stereotyped patterns of cell shape change, rearrangement and tissue deformation that accompany formation of the notochord and neural tube?

Selected Publications

Chen W, Hu Y, Lang CF, Brown JS, Schwabach S, Song X, Zhang Y, Munro E, Bennett K, Zhang D, Lee HC. 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. 

Weirich KL, Stam S, Munro E, Gardel ML. Actin bundle architecture and mechanics regulate myosin II force generation. Biophys J. 2021 05 18; 120(10):1957-1970. 

Lenne PF, Munro E, Heemskerk I, Warmflash A, Bocanegra-Moreno L, Kishi K, Kicheva A, Long Y, Fruleux A, Boudaoud A, Saunders TE, Caldarelli P, Michaut A, Gros J, Maroudas-Sacks Y, Keren K, Hannezo E, Gartner ZJ, Stormo B, Gladfelter A, Rodrigues A, Shyer A, Minc N, Maître JL, Di Talia S, Khamaisi B, Sprinzak D, Tlili S. Roadmap for the multiscale coupling of biochemical and mechanical signals during development. Phys Biol. 2021 Apr 14; 18(4). 

Godard BG, Dumollard R, Munro E, Chenevert J, Hebras C, McDougall A, Heisenberg CP. Apical Relaxation during Mitotic Rounding Promotes Tension-Oriented Cell Division. Dev Cell. 2020 12 21; 55(6):695-706.e4. 

Chen W, Hu Y, Lang CF, Brown JS, Schwabach S, Song X, Zhang Y, Munro E, Bennett K, Zhang D, Lee HC. 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. 

Cavanaugh KE, Staddon MF, Munro E, Banerjee S, Gardel ML. RhoA Mediates Epithelial Cell Shape Changes via Mechanosensitive Endocytosis. Dev Cell. 2020 01 27; 52(2):152-166.e5. 

Hashimoto H, Munro E. 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.

Staddon MF, Cavanaugh KE, Munro EM, Gardel ML, Banerjee S. Mechanosensitive Junction Remodeling Promotes Robust Epithelial Morphogenesis. Biophys J. 2019 11 05; 117(9):1739-1750. 

Bailles A, Collinet C, Philippe JM, Lenne PF, Munro E, Lecuit T. Genetic induction and mechanochemical propagation of a morphogenetic wave. Nature. 2019 08; 572(7770):467-473. 

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

Michaux JB, Robin FB, McFadden WM, Munro EM. Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo. J Cell Biol. 2018 12 03; 217(12):4230-4252. 

Wu Y, Han B, Li Y, Munro E, Odde DJ, Griffin EE. 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.

Hashimoto H, Munro E. Dynamic interplay of cell fate, polarity and force generation in ascidian embryos. Curr Opin Genet Dev. 2018 08; 51:67-77. 

McFadden WM, McCall PM, Gardel ML, Munro EM. 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.