Embryonic wound repair provides an excellent model to investigate collective cell movements. Embryonic wound healing is
driven by the coordinated migration of the cells around the
wound into the damaged region, in a process conserved across
species, from fruit flies to mice [4–8]. Wound healing in embryos
does not involve cell division, and occurs in the absence of an
inflammatory response. Thus, the study of embryonic wound repair
allows researchers to specifically address and understand the
mechanisms that drive coordinated cell movements. Embryonic
wound closure can be imaged live in several organisms, provides
an easy way to register experiments based on the time of wounding,
and occurs rapidly (a few minutes to 1–2 h). Together, all these
features facilitate the use of quantitative methods to analyze embryonic wound healing and increase the statistical power of the
analyses.
The collective cell movements that drive wound
re-epithelization are associated with a partial epithelial-to-mesenchymal transition (EMT). EMT is characterized by changes in
molecular composition and cell behavior that are also present during embryonic wound repair. For example, in classical models of
EMT, such as gastrulation in mouse embryos, or cancer cell invasion, E-cadherin-based adherens junctions are dramatically reorganized to facilitate cell movements [9, 10]. Similar junctional
rearrangements also occur during embryonic wound closure [11–
13]. EMT events are often partial, with cells retaining some degree
of collectiveness. Thus, groups of cells undergoing EMT can establish a front-back axis of polarity within the group. The cells at the
front exhibit increased protrusive activity in comparison to “follower cells” [14]. The front-to-back axis of polarity is also found in
embryonic wound healing, with cells at the wound edge displaying
an increased number of actin-based protrusions [15, 16]. Collective
invasion by squamous cell carcinoma cells is associated with the
assembly of a cable formed by actin and the molecular motor
non-muscle myosin II around the group of invading cells [17]. Similarly, actin and myosin become polarized in the cells at the wound
edge and accumulate at the interface with the wounded cells
[15, 18], assembling an actomyosin cable that coordinates cell
movements to drive rapid wound closure [15, 19, 20]. Thus, elucidating the mechanisms of coordinated cell migration during
wound closure will increase our understanding of how EMT and
collective cell movements contribute to embryonic development
and the spread of disease in vivo.
Advances in microscopy have pushed the limits of our understanding of coordinated cell movements to shorter time and length
scales. Spinning disk confocal microscopy, for example, overcomes
the speed limitations of laser scanning confocal microscopy by
illuminating multiple points in the field of view simultaneously
[21]. Photons emitted by the sample can be collected more
200
Gordana Scepanovic et al.
driven by the coordinated migration of the cells around the
wound into the damaged region, in a process conserved across
species, from fruit flies to mice [4–8]. Wound healing in embryos
does not involve cell division, and occurs in the absence of an
inflammatory response. Thus, the study of embryonic wound repair
allows researchers to specifically address and understand the
mechanisms that drive coordinated cell movements. Embryonic
wound closure can be imaged live in several organisms, provides
an easy way to register experiments based on the time of wounding,
and occurs rapidly (a few minutes to 1–2 h). Together, all these
features facilitate the use of quantitative methods to analyze embryonic wound healing and increase the statistical power of the
analyses.
The collective cell movements that drive wound
re-epithelization are associated with a partial epithelial-to-mesenchymal transition (EMT). EMT is characterized by changes in
molecular composition and cell behavior that are also present during embryonic wound repair. For example, in classical models of
EMT, such as gastrulation in mouse embryos, or cancer cell invasion, E-cadherin-based adherens junctions are dramatically reorganized to facilitate cell movements [9, 10]. Similar junctional
rearrangements also occur during embryonic wound closure [11–
13]. EMT events are often partial, with cells retaining some degree
of collectiveness. Thus, groups of cells undergoing EMT can establish a front-back axis of polarity within the group. The cells at the
front exhibit increased protrusive activity in comparison to “follower cells” [14]. The front-to-back axis of polarity is also found in
embryonic wound healing, with cells at the wound edge displaying
an increased number of actin-based protrusions [15, 16]. Collective
invasion by squamous cell carcinoma cells is associated with the
assembly of a cable formed by actin and the molecular motor
non-muscle myosin II around the group of invading cells [17]. Similarly, actin and myosin become polarized in the cells at the wound
edge and accumulate at the interface with the wounded cells
[15, 18], assembling an actomyosin cable that coordinates cell
movements to drive rapid wound closure [15, 19, 20]. Thus, elucidating the mechanisms of coordinated cell migration during
wound closure will increase our understanding of how EMT and
collective cell movements contribute to embryonic development
and the spread of disease in vivo.
Advances in microscopy have pushed the limits of our understanding of coordinated cell movements to shorter time and length
scales. Spinning disk confocal microscopy, for example, overcomes
the speed limitations of laser scanning confocal microscopy by
illuminating multiple points in the field of view simultaneously
[21]. Photons emitted by the sample can be collected more
200
Gordana Scepanovic et al.