cell news 2/2013
4
binder innovation prize
forces and fows:
actomyosin ring function in zebrafsh epiboly
Martin behrndt
1,2
and stephan w. grill
1,3
1
Mpi-pks, am campus 1, 3400 klosterneuburg, austria
2
ist austria, pfotenhauer str. 108, 01307 dresden, germany
3
Mpi-cbg, nöthnitzer str. 38, 01187 dresden, germany
Introduction
The development of an embryo from a single cell into a com-
plex organism is accompanied by a rich variety of morphogenetic
events. Tissues have to spread, fold or contract in a precisely
patterned scheme to ensure the functioning form of the embryo.
On a molecular scale flamentous actin and non-muscle myo-
sin-2 have been characterized early on as key players involved in
cell and tissue morphogenesis
(1, 2)
. Together with a myriad of
other components they form a dense meshwork that comprises
the actomyosin cortex
(3-5)
. While this network promotes sha-
pe changes on the cellular and tissue scale, the mechanisms of
force generation through actomyosin networks remain unresol-
ved in most instances. Only recently have advances in imaging
and force probing techniques allowed to gain a better mechani-
stic insight into how molecular forces integrate into cell and tis-
sue deformation and fow
(6-8)
. For example, during
Drosophila
germband elongation orientation-specifc enrichment of myo-
sin-2 at cellular boundaries of the epithelium drives junctional
remodeling in a local cell intercalation process, which integrates
on the tissue scale to an effective elongation of the epithelium
(9)
. In zebrafsh gastrulation down-regulation of the actomyosin
cortex at cellular contacts control contact expansion and pro-
mote in an interplay with differential adhesion cell sorting for
the establishment of distinct germ layers
(10).
How myosin contractile activity generates fow is best under-
stood in the
C. elegans
zygote. Newton’s laws must be obeyed at
all scales, and fows are associated with mechanical tension in
the cortex. Importantly, force generation at the molecular sca-
le through the activity of non-muscle myosin-2 can give rise
to isotropic active tension (also referred to as contractility). An
imbalance in myosin concentration generates a gradient in ac-
tive tension in the direction in which myosin concentration is
changing. The active tension gradient in turn drives actomyosin
cortical fow in a manner akin to how pressure gradients drive
Stokes’ fow in a highly viscous fuid
(11, 12)
. A fuid description
is appropriate because cortical constituents turn over multiple
times during fow, rendering the material effectively viscous. It is
important to identify and measure mesoscale physical properties
of the cortex, since they determine the behavior of the cortex
at larger scales. For example, cortical viscosity determines over
what distance myosin activity can drive fow
(11)
.
While some aspects of actomyosin mechanics at larger scales
have been identifed, much remains to be explained. For examp-
le, apical constriction in the presumptive mesoderm of
Droso-
phila
embryos does not occur as previously thought through a
continuous contraction processes of cortical junctions, but is
mediated through contractive pulses of the apical actomyosin
network
(13)
. What governs the period of these pulsatile acto-
myosin fows and how the fows translate into effective force
generation on the tissue scale, remain exciting open questions.
For example, in
C. elegans
gastrulation, a molecular clutch me-
chanism has been explored in which actomyosin fows at the
apical cortex of endodermal precursor cells precede the actual
shrinkage of the apical surface. Only upon mechanically coupling
the centripedal cortical fows through a cadherin-catenin com-
plex to the cellular junctions, actomyosin contraction is effci-
ently translated into cellular shape changes, eventually trigge-
ring endodermal internalization through apical constriction
(14)
.
A full understanding of actomyosin dynamics and mechanics can
only be provided when all relevant mesoscale physical properties
have been identifed by theory and measured in experiments, and
their relation with deformation and fow have been characte-
rized by theory and tested in experiments. This will be a challen-
ging task given the wealth of different morphological processes.
Nevertheless, it will be essential to fnd unifying themes to bring
us a step closer to understand how biological form is controlled
during embryonic development.
In this article we will focus on the frst major morphogenetic mo-
vement in the life of a zebrafsh embryo, the epiboly movement.
This is a particular exciting example of tissue morphogenesis as
it involves the concerted spreading of an epithelial tissue and an
adjacent actomyosin structure of embryonic dimension, which
is situated within a continuous syncytium. To some extent, epi-
