The Faculty

Focus

How the dynamics of embryonic cell and tissue behavior emerge through the interplay between regulatory biochemistry, cytoskeletal dynamics and cytomechanics

Education

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

BPHYS Student

William McFadden

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

Munro EM, Shupe LE, and Fetz EE (1994) Integration and differentiation in dynamic recurrent neural networks. Neural Comp 6: 405-419.

Von Dassow G, Meir E, b and Odell GM (2000) The segment polarity network is a robust developmental module. Nature 406(6792): 188-192.

Munro EM and Odell GM  (2002) Polarized basolateral cell motility underlies invagination and convergent extension of the ascidian notochord plate. Development 129(1): 13-24.

Munro EM and Odell GM  (2002) Morphogenetic pattern formation during ascidian notochord formation is regulative and highly robust.  Development 129(1): 1-12.

Meir E, von Dassow G, Munro EM, and Odell GM (2002) Robustness, flexibility, and the role of lateral inhibition in the neurogenic network.  Current Biology 12(10): 778-86.

Meir E, Munro EM, Odell GM and von Dassow G (2002) Ingeneue, a versatile tool for reconstituting genetic networks in silico. J Exp Zool. (Mol. Dev. Evol.) 294:216-51.

Nance J, Munro EM and Priess JR (2003) C. elegans PAR-3 and PAR-6 are required for apicobasal asymmetries associated with cell adhesion and gastrulation. Development 130:5339-50.

Munro E, Nance J and Priess JR (2004) Cortical flows powered by asymmetrical contraction transport PAR proteins to establish and maintain anterior-posterior polarity in the early C. elegans embryo. Dev Cell 7: 413-24.

Jiang D, Munro EM and Smith WC (2005) Ascidian prickle regulates both mediolateral and anterior-posterior cell polarity of notochord cells. Curr Biol. 15:79-85.

Willis JH, Munro EM, Lyczak R and Bowerman B (2006) Conditional dominant mutations in the C. elegans gene act-2 identify cytoplasmic and muscle roles for a redundant actin isoform.  Mol Biol Cell. 17(3):1051-64. PMCID: PMC1382297

Warner M, Munro EM* and Glotzer M (2007) Astral microtubules spatially bias cortical myosin recruitment to break symmetry and promote cytokinesis. Curr Biol, 17(15):1286–1297. *co-senior author.

Baruni JK, Munro, EM, and von Dassow G (2008) Cytokinetic furrowing in toroidal, binucleate, and anucleate cells in C. elegans embryos. J Cell Science 121(3): 306-16.

Gallo CM, Munro EM, Rasoloson D, Merritt C, and Seydoux G (2008) Processing bodies and germ granules are distinct cytoplasmic granules that interact in C. elegans embryos.  Dev Biol 323(1):76-87.

Shi, W, Peyrot, S, Munro, EM, and Levine, M (2009).  FGF3 in the floorplate directs notochord convergent extension in the Ciona tadpole.  Development 36(1):23-8. PMCID: PMC2685959

Sherrard, KM, Robin FR, Lemaire, P, and Munro EM. Sequential activation of apical and basolateral contractility drives ascidian endoderm invagination.  Curr Biol  [PubMed - in process]