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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?
Shi, W, Peyrot, S, Munro, EM, and
Levine, M (2009) FGF3 in the floorplate directs notochord convergent
extension in the Ciona tadpole. Development 2009 136(1):23-8. (PubMed)
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. (PubMed)
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. (PubMed)
Munro EM (2007) The microtubules
dance and the spindle poles swing. Cell. 129(3): 457-8. (Review)
(PubMed)
Munro EM (2007) Asymmetric cell division:
a CAB driver for spindle movements. Curr Biol. 17(16):R639-41. (Review)
(PubMed)
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.
(PubMed)
Munro EM, Robin F, and Lemaire P
(2006) Cellular Morphogenesis in Ascidians. Current Opinion in Genetics
and Development; 16(4):399-405. (Review) (PubMed)
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. (PubMed)
Munro EM (2006) Par proteins and
the cytoskeleton: A marriage of equals. Current Opinion in Cell
Biology. 18(1): 86-94. (Review) (PubMed)
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. (PubMed)
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