Wound-induced assembly and closure of an actomyosin purse string in Xenopus oocytes.

BACKGROUND: Both single cells and multicellular systems rapidly heal physical insults but are thought to do so by distinctly different mechanisms. Wounds in single cells heal by calcium-dependent membrane fusion, whereas multicellular wounds heal by a variety of different mechanisms, including circumferential contraction of an actomyosin 'purse string' that assembles around wound borders and is dependent upon the small GTPase Rho. RESULTS: We investigated healing of puncture wounds made in Xenopus oocytes, a single-cell system. Oocyte wounds rapidly assumed a circular morphology and constricted circumferentially, coincident with the recruitment of filamentous actin (F-actin) and myosin-II to the wound borders. Surprisingly, recruitment of myosin-II to wound borders occurred before that of F-actin. Further, experimental disruption of F-actin prevented healing but did not prevent myosin-II recruitment. Actomyosin purse-string assembly and closure was dependent on Rho GTPases and extracellular calcium. Wounding resulted in reorganization of microtubules into an array similar to that which forms during cytokinesis in Xenopus embryos. Experimental perturbation of oocyte microtubules before wounding inhibited actomyosin recruitment and wound closure, whereas depolymerization of microtubules after wounding accelerated wound closure. CONCLUSIONS: We conclude the following: actomyosin purse strings can close single-cell wounds; myosin-II is recruited to wound borders independently of F-actin; purse-string assembly is dependent on a Rho GTPase; and purse-string assembly and closure are controlled by microtubules. More generally, the results indicate that actomyosin purse strings have been co-opted through evolution to dispatch a broad variety of single-cell and multicellular processes, including wound healing, cytokinesis and morphogenesis.     

Signaling pathways and cell mechanics involved in wound closure by epithelial cell sheets

BACKGROUND: Sheets of cells move together as a unit during wound healing and embryonic tissue movements, such as those occurring during gastrulation and neurulation. We have used epithelial wound closure as a model system for such movements and examined the mechanisms of closure and the importance of the Rho family of Ras-related small GTPases in this process. RESULTS: Wounds induced in Madin-Darby canine kidney (MDCK) epithelial cell monolayers close by Rac- and phosphoinositide-dependent cell crawling, with formation of lamellipodia at the wound margin, and not by contraction of a perimarginal actomyosin purse-string. Although Rho-dependent actin bundles usually form at the margin, neither Rho activity nor formation of these structures is required for wound closure to occur at a normal rate. Cdc42 activity is also not required for closure. Inhibition of Rho or Cdc42 results, however, in statistically significant decreases in the regularity of wound closure, as determined by the ratio of wound margin perimeter over the remaining denuded area at different times. The Rac-dependent force generation for closure is distributed over several rows of cells from the wound margin, as inhibition of motility in the first row of cells alone does not inhibit closure and can be compensated for by generation of motile force in cells behind the margin. Furthermore, we observed high levels of Rac-dependent actin assembly in the first few rows of cells from the wound margin. CONCLUSIONS: Wounds in MDCK cell sheets do not close by purse-string contraction but by a crawling behavior involving Rac, phosphoinositides and active movement of multiple rows of cells. This finding suggests a new distributed mode of signaling and movement that, nevertheless, resembles individual cell motility. Although Rho and Cdc42 activities are not required for closure, they have a role in determining the regularity of closure.     

Healing of incisional wounds in the embryonic chick wing bud: characterization of the actin purse-string and demonstration of a requirement for Rho activation

Small skin wounds in the chick embryo do not heal by lamellipodial crawling of cells at the wound edge as a skin wound does in the adult, but rather by contraction of an actin purse-string that rapidly assembles in the front row of epidermal cells (Martin, P., and J. Lewis. 1992. Nature (Lond.). 360:179-183). To observe the early time course of actin purse-string assembly and to characterize other cytoskeletal components of the contractile machinery, we have followed the healing of incisional or slash wounds on the dorsum of the chick wing; these wounds take only seconds to create and heal within approximately 6 h. Healing of the epithelium depends on a combination of purse-string contraction and zipper-like closure of the gap between the cut edges of the epithelium. Confocal laser scanning microscope studies show that actin initially aligns into a cable at the wound margin in the basal layer of the epidermis within approximately 2 min of wounding. Coincident with actin cable assembly, we see localization of cadherins into clusters at the wound margin, presumably marking the sites where segments of the cable in adjacent cells are linked via adherens junctions. A few minutes later we also see localization of myosin II at the wound margin, as expected if myosin is being recruited into the cable to generate a contractile force for wound healing. At the time of wounding, cells at the wound edge become transiently leaky, allowing us to load them with reagents that block the function of two small GTPases, Rho and Rac, which recently have been shown to play key roles in reorganiztion of the actin cytoskeleton in tissue-culture cells (Hall, A. 1994. Annu. Rev. Cell Biol. 10:31-54). Loading wound edge epidermal cells with C3 transferase, a bacterial exoenzyme that inactivates endogenous Rho, prevents assembly of an actin cable and causes a failure of healing. No such effects are seen with N17rac, a dominant inhibitory mutant Rac protein. These findings support the view that in this system the actin cable is required for healing-both the purse-string contraction and the zipping up-and that Rho is required for formation of the actin cable.     

Pattern and morphogenesis of presumptive superficial mesoderm in two closely related species, Xenopus laevis and Xenopus tropicalis

The mesoderm, comprising the tissues that come to lie entirely in the deep layer, originates in both the superficial epithelial and the deep mesenchymal layers of the early amphibian embryo. Here, we characterize the mechanisms by which the superficial component of the presumptive mesoderm ingresses into the underlying deep mesenchymal layer in Xenopus tropicalis and extend our previous findings for Xenopus laevis. Fate mapping the superficial epithelium of pregastrula stage embryos demonstrates ingression of surface cells into both paraxial and axial mesoderm (including hypochord), in similar patterns and amounts in both species. Superficial presumptive notochord lies medially, flanked by presumptive hypochord and both overlie the deep region of the presumptive notochord. These tissues are flanked laterally by superficial presumptive somitic mesoderm, the anterior tip of which also appears to overlay the presumptive deep notochord. Time-lapse recordings show that presumptive somitic and notochordal cells move out of the roof of the gastrocoel and into the deep region during neurulation, whereas hypochordal cells ingress after neurulation. Scanning electron microscopy at the stage and position where ingression occurs suggests that superficial presumptive somitic cells in X. laevis ingress into the deep region as bottle cells whereas those in X. tropicalis ingress by "relamination" (e.g., [Dev. Biol. 174 (1996) 92]). In both species, the superficially derived presumptive somitic cells come to lie in the medial region of the presumptive somites during neurulation. By the early tailbud stages, these cells lie at the horizontal myoseptum of the somites. The morphogenic pathway of these cells strongly resembles that of the primary slow muscle pioneer cells of the zebrafish. We present a revised fate map of Xenopus, and we discuss the conservation of superficial mesoderm within amphibians and across the chordates and its implications for the role of this tissue in patterning the mesoderm.     

Wound healing ability of Xenopus laevis embryos. II. Morphological analysis of wound marginal epidermis

We previously showed that bisectional wounds made in Xenopus laevis embryos at the primary eye vesicle stage were rapidly closed. In this study, microscopic analyses, including scanning electron microscopy, on the morphology of the epidermis were conducted during wound closure in the half embryos. Bright fluorescence of Texas red-phalloidin showing actin filaments started to be visualized at the cut edge 10 min after wounding. It increased with time, forming a distinguished, though discontinuous, bundle along the wound margin. The wound closure was completely inhibited by 20 microm cytochalasin B, and almost completely by 50 mm 2,3-butanedione 2-monoxime, an inhibitor to myosin ATPase activity. Scanning electron microscopy revealed that the outer epidermal cells became extensively elongated in the radial direction, and the contour of the closing wound edge did not become smoother but remained ragged. Thus, a representative embryonic type of wound closure may be driven in Xenopus embryos by a complex mechanism, involving not only the actin 'purse-string' but also an inward movement of individual cells. Anyhow, the wound closure is a movement of the epidermal sheet maintaining cell-cell contact, and not involving locomotion of single cells separated from the wound edge.     

Effects of calcium antagonists and calcium-buffered salines on wound healing in Xenopus early embryos

The role of calcium in the process of wound closure in Xenopus early embryos was studied. Embryos were wounded in the presence of the calcium antagonists D-600 and TMB-8 or in calcium-buffered salines, and the effects on wound healing were observed by scanning electron microscopy. D-600 and TMB-8 inhibit wound closure and these antagonists appear to act synergistically since their combined effect is greater than their individual effects. Experiments with calcium-buffered salines suggest that wound closure can proceed in the presence of low extracellular calcium. In all conditions there is a correlation between the degree of wound closure and the shapes of the cells at the wound margin; closing wounds are accompanied by cells elongated radial to the wound, gaping (non-closing) wounds are accompanied by cells stretched tangential to the wound. Thus the results suggest that calcium influx may not be a requirement for the changes in cell shape which accompany, and probably effect, wound closure in Xenopus early embryos.     

Exposure to external environment of low ion concentrations is the trigger for rapid wound closure in Xenopus laevis embryos

Wounds in Xenopus laevis embryos close rapidly, as previously described. In this study, we examined the dependence on extracellular Na(+) and/or Cl(-) ion concentrations of the closure of wounds in Xenopus embryos inflicted by thermal injury. Wound closure did not occur in normal amphibian medium (100% NAM), while wound areas remarkably decreased either in 10-50% NAM or in 100% NAM lacking Na(+) or Cl(-). Similarly, wound areas did not change in a set of Na(+) and Cl(-) ion concentrations equivalent to those of the humoral fluids of intact Xenopus embryos, but rapid wound closure was induced by decreasing the concentration of either of the two ions. A tangential accumulation of actin cytoskeleton along the wound edge was associated with wound closure. However, a similar actin alignment formed even under the 100% NAM condition, in which wounds did not close, as stated above. The epidermis around the wound edge exhibited ellipse-shaped hypertrophy, and the marginal cells centripetally elongated during wound closure. On the other hand, no distinct morphological changes occurred in 100% NAM, although the epidermis was somewhat thickened. Thus, the morphological changes in the epidermis specific to the low ionic environment most likely play active roles in the wound closure of Xenopus laevis embryos, whereas the tangential actin alignment alone may be insufficient. Taken together, we propose that the wound closure in Xenopus embryos is triggered by a decline in either the extracellular Na(+) or Cl(-) ion concentration, and that this process is required for the abovementioned changes in the shape of the marginal cells.     

Wound closure in the lamellipodia of single cells: mediation by actin polymerization in the absence of an actomyosin purse string

The actomyosin purse string is an evolutionarily conserved contractile structure that is involved in cytokinesis, morphogenesis, and wound healing. Recent studies suggested that an actomyosin purse string is crucial for the closure of wounds in single cells. In the present study, morphological and pharmacological methods were used to investigate the role of this structure in the closure of wounds in the peripheral cytoplasm of sea urchin coelomocytes. These discoidal shaped cells underwent a dramatic form of actin-based centripetal/retrograde flow and occasionally opened and closed spontaneous wounds in their lamellipodia. Fluorescent phalloidin staining indicated that a well defined fringe of actin filaments assembles from the margin of these holes, and drug studies with cytochalasin D and latrunculin A indicated that actin polymerization is required for wound closure. Additional evidence that actin polymerization is involved in wound closure was provided by the localization of components of the Arp2/3 complex to the wound margin. Significantly, myosin II immunolocalization demonstrated that it is not associated with wound margins despite being present in the perinuclear region. Pharmacological evidence for the lack of myosin II involvement in wound closure comes from experiments in which a microneedle was used to produce wounds in cells in which actomyosin contraction was inhibited by treatment with kinase inhibitors. Wounds produced in kinase inhibitor-treated cells closed in a manner similar to that seen with control cells. Taken together, our results suggest that an actomyosin purse string mechanism is not responsible for the closure of lamellar wounds in coelomocytes. We hypothesize that the wounds heal by means of a combination of the force produced by actin polymerization alone and centripetal flow. Interestingly, these cells did assemble an actomyosin structure around the margin of phagosome-like membrane invaginations, indicating that myosin is not simply excluded from the periphery by some general mechanism. The results indicate that the actomyosin purse string is not the only mechanism that can mediate wound closure in single cells.     

Possible roles of ENaC and Cl(-) channel in wound closure in Xenopus laevis embryos

Our previous report showed that rapid wound closure in Xenopus laevis embryos was associated with a decrease in the extracellular concentration of either Na(+) or Cl(-) ions. In this study, we examined the wound closure in Xenopus embryos when epithelial Na(+) channel (ENaC), Na(+)/K(+) ATPase (Na(+) pump) or CICs (members of Cl(-) channel) were blocked by each specific inhibitor. Blockage of ENaC and CIC restricted the rate of wound closure during the first 30 min PW and during the subsequent period, respectively. In contrast, inhibition of Na(+) pump had no effect on the rate of wound closure. Furthermore, simultaneous administration of both ENaC and CIC inhibitors resulted in the cumulative reduction of wound closure. Thus, it is plausible that these ion channels play active roles in wound closure in Xenopus embryos. NPPB is known to inhibit both CIC-2 and CIC-3. Immunohistochemical experiments showed that CIC-3, but not CIC-2, was expressed in Xenopus embryos, suggesting that the reduced wound closure by NPPB was due to blockage of CIC-3. A local enhancement of CIC-3 expression at the leading edge of the wounded epidermis was found to be specific to closing wounds that were kept in 10% NAM. An in vitro wounding assay also showed a pattern of CIC-3 expression at the margin of the scratch wound comparable to the results in vivo. These findings suggest that intracellular translocation of CIC-3 is involved in wound closure. We propose that the ion channels, including CIC-3, play a crucial role in wound closure in Xenopus embryos.     

PAR1 specifies ciliated cells in vertebrate ectoderm downstream of aPKC

Partitioning-defective 1 (PAR1) and atypical protein kinase C (aPKC) are conserved serine/threonine protein kinases implicated in the establishment of cell polarity in many species from yeast to humans. Here we investigate the roles of these protein kinases in cell fate determination in Xenopus epidermis. Early asymmetric cell divisions at blastula and gastrula stages give rise to the superficial (apical) and the deep (basal) cell layers of epidermal ectoderm. These two layers consist of cells with different intrinsic developmental potential, including superficial epidermal cells and deep ciliated cells. Our gain- and loss-of-function studies demonstrate that aPKC inhibits ciliated cell differentiation in Xenopus ectoderm and promotes superficial cell fates. We find that the crucial molecular substrate for aPKC is PAR1, which is localized in a complementary domain in superficial ectoderm cells. We show that PAR1 acts downstream of aPKC and is sufficient to stimulate ciliated cell differentiation and inhibit superficial epidermal cell fates. Our results suggest that aPKC and PAR1 function sequentially in a conserved molecular pathway that links apical-basal cell polarity to Notch signaling and cell fate determination. The observed patterning mechanism may operate in a wide range of epithelial tissues in many species.     

Specific signaling cascades involved in cell spreading during healing of micro-wounded gastric epithelial monolayers

Mechanisms that specifically modulate cell spreading and/or cell migration following epithelial wounding are poorly understood. Using micro-wounded human gastric epithelial monolayers, we show herein that EGF and TGFalpha maximally increase spreading of epithelial sheets under a cell proliferation-independent mechanism. Treatment of confluent HGE-17 cells with the phosphatidylinositol 3-kinase inhibitor, LY294002, and the epidermal growth factor receptor inhibitor, PD153035, strongly reduced basal and TGFalpha-stimulated cell spreading. While pharmacological inhibition of pp60src-kinase activity also attenuated basal epithelial spreading, addition of the mTOR/p70S6K inhibitor rapamycin or a specific siRNA targeting ILK sequence did not affect the kinetic rates of wound closure. Epithelial wound healing was initiated by actin purse-string contraction followed by lamellae formation. Conversely, disruption of actin and tubulin stability with cytochalasin D and nocodazole, respectively, inhibited epithelial sheet spreading. Finally, antibodies directed against the alpha3 integrin subunit, but not against the alpha6 or alpha2 subunits, attenuated epithelial sheet spreading as well as lamellae formation. In conclusion, the current investigation establishes that EGF/TGFalpha and the alpha3beta1 integrin, pp60c-src, EGFR and PI3K pathways are mainly associated with the cell spreading of the restitution process during healing of human gastric epithelial wounds.     

Multiple forces contribute to cell sheet morphogenesis for dorsal closure in Drosophila

The molecular and cellular bases of cell shape change and movement during morphogenesis and wound healing are of intense interest and are only beginning to be understood. Here, we investigate the forces responsible for morphogenesis during dorsal closure with three approaches. First, we use real-time and time-lapsed laser confocal microscopy to follow actin dynamics and document cell shape changes and tissue movements in living, unperturbed embryos. We label cells with a ubiquitously expressed transgene that encodes GFP fused to an autonomously folding actin binding fragment from fly moesin. Second, we use a biomechanical approach to examine the distribution of stiffness/tension during dorsal closure by following the response of the various tissues to cutting by an ultraviolet laser. We tested our previous model (Young, P.E., A.M. Richman, A.S. Ketchum, and D.P. Kiehart. 1993. Genes Dev. 7:29-41) that the leading edge of the lateral epidermis is a contractile purse-string that provides force for dorsal closure. We show that this structure is under tension and behaves as a supracellular purse-string, however, we provide evidence that it alone cannot account for the forces responsible for dorsal closure. In addition, we show that there is isotropic stiffness/tension in the amnioserosa and anisotropic stiffness/tension in the lateral epidermis. Tension in the amnioserosa may contribute force for dorsal closure, but tension in the lateral epidermis opposes it. Third, we examine the role of various tissues in dorsal closure by repeated ablation of cells in the amnioserosa and the leading edge of the lateral epidermis. Our data provide strong evidence that both tissues appear to contribute to normal dorsal closure in living embryos, but surprisingly, neither is absolutely required for dorsal closure. Finally, we establish that the Drosophila epidermis rapidly and reproducibly heals from both mechanical and ultraviolet laser wounds, even those delivered repeatedly. During healing, actin is rapidly recruited to the margins of the wound and a newly formed, supracellular purse-string contracts during wound healing. This result establishes the Drosophila embryo as an excellent system for the investigation of wound healing. Moreover, our observations demonstrate that wound healing in this insect epidermal system parallel wound healing in vertebrate tissues in situ and vertebrate cells in culture (for review see Kiehart, D.P. 1999. Curr. Biol. 9:R602-R605).     

Wound healing ability of Xenopus laevis embryos. I. Rapid wound closure achieved by bisectional half embryos

We examined wound closure in 'half embryos' produced by the transverse bisection of Xenopus laevis embryos at the primary eye vesicle stage. Both the anterior- and posterior-half embryos survived for more than 6 days, and grew into 'half tadpoles'. Histology and videomicroscopy revealed that the open wound in the half embryo was rapidly closed by an epithelial sheet movement in the wound marginal zone. The time-course of wound closure showed a downward convex curve: the wound area decreased to one-fifth of the original area within 30 min, and the wound continued to contract slowly thereafter. The rapidity of closure of the epidermis as well as the absence of inflammatory cells are typical features of an embryonic type of wound healing. There was a dorso-ventral polarity in the motility of the epidermis: the wound was predominantly closed by the ventral and lateral epidermis. The change in the contour of the wound edge with time suggested a complex mechanism involved in the wound closure that could not be explained only by the purse-string theory. The present experimental system would be a unique and useful model for analyses of cellular movements in the embryonic epithelia.     

Homoiogenetic Neural Inducing Activity of the Presumptive Neural Plate of Xenopus Laevis

Heteroplastic combinations were made between Xenopus laevis presumptive neural plate and competent ectoderm of Xenopus borealis . Primarily induced presumptive neural plate cells ( Xenopus laevis ) can easily be distinguished from Xenopus borealis cells by specific quinacrine fluorescence of the nuclei. It was clearly shown that presumptive neural plate, which has primarily been induced by the underlying chordamesoderm exerts homoiogenetic inducing activity on competent ectoderm. The inducing activity is increased in pieces of presumptive neural plates, when the superficial layer has been removed from the adjacent deep layers. The enhancement can be explained by the fact that the removal of the superficial layer acting as barrier allows the inducing stimulus to be easily propagated from the apical (distal) side of the deep layers of the presumptive neural plate.     

Wounded cells drive rapid epidermal repair in the early Drosophila embryo

Epithelial tissues are protective barriers that display a remarkable ability to repair wounds. Wound repair is often associated with an accumulation of actin and nonmuscle myosin II around the wound, forming a purse string. The role of actomyosin networks in generating mechanical force during wound repair is not well understood. Here we investigate the mechanisms of force generation during wound repair in the epidermis of early and late Drosophila embryos. We find that wound closure is faster in early embryos, where, in addition to a purse string around the wound, actomyosin networks at the medial cortex of the wounded cells contribute to rapid wound repair. Laser ablation demonstrates that both medial and purse-string actomyosin networks generate contractile force. Quantitative analysis of protein localization dynamics during wound closure indicates that the rapid contraction of medial actomyosin structures during wound repair in early embryos involves disassembly of the actomyosin network. By contrast, actomyosin purse strings in late embryos contract more slowly in a mechanism that involves network condensation. We propose that the combined action of two force-generating structures—a medial actomyosin network and an actomyosin purse string—contributes to the increased efficiency of wound repair in the early embryo.     

Effects of mutant rat dynamin on endocytosis

The process of wound repair in monolayers of the intestinal epithelial cell line, Caco-2BBe, was analyzed by a combination of time-lapse differential interference contrast (DIC) video and immunofluorescence microscopy, and laser scanning confocal immunofluorescence microscopy (LSCIM). DIC video analysis revealed that stab wounds made in Caco-2BBe monolayers healed by two distinct processes: (a) Extension of lamellipodia into the wounds; and (b) Purse string closure of the wound by distinct arcs or rings formed by cells bordering the wound. The arcs and rings which effected purse string closure appeared sharp and sheer in DIC, spanned between two and eight individual cells along the wound border, and contracted in a concerted fashion. Immunofluorescence analysis of the wounds demonstrated that the arcs and rings contained striking accumulations of actin filaments, myosin-II, villin, and tropomyosin. In contrast, arcs and rings contained no apparent enrichment of microtubules, brush border myosin-I immunogens, or myosin- V. LSCIM analysis confirmed the localization of actin filaments, myosin- II, villin, and tropomyosin in arcs and rings at wound borders. ZO-1 (a tight junction protein), also accumulated in arcs and rings around wounds, despite the fact that cell-cell contacts are absent at wound borders. Sucrase-isomaltase, an apically-localized integral membrane protein, maintained an apical localization in cells where arcs or rings were formed, but was found in lamellipodia extending into wounds in cells where arcs failed to form. Time-course, LSCIM quantification of actin, myosin II, and ZO-1 revealed that accumulation of these proteins within arcs and rings at the wound edge began within 5 minutes and peaked within 30-60 minutes of wounding. Actin filaments, myosin-II, and ZO-1 achieved 10-, 3-, and 4-fold enrichments, respectively, relative to cell edges which did not border wounds. The results demonstrate that wounded Caco-2BBe monolayers assemble a novel cytoskeletal structure at the borders of wounds. The results further suggest that this structure plays at least two roles in wound repair; first, mediation of concerted, purse string movement of cells into the area of the wound and second, maintenance of apical/basolateral polarity in cells which border the wound.     

Mesoderm layer formation in Xenopus and Drosophila gastrulation

During gastrulation, the mesoderm spreads out between ectoderm and endoderm to form a mesenchymal cell layer. Surprisingly the underlying principles of mesoderm layer formation are very similar in evolutionarily distant species like the fruit fly, Drosophila melanogaster, and the frog, Xenopus laevis, in which the molecular and the cellular basis of mesoderm layer formation have been extensively studied. Complementary expression of growth factors in the ectoderm and their receptors in the mesoderm act to orient cellular protrusive activities and direct cell movement, leading to radial cell intercalation and the spreading of the mesoderm layer. This mechanism is contrasted with generic physical mechanisms of tissue spreading that consider the adhesive and physical properties of the cells and tissues. Both mechanisms need to be integrated to orchestrate mesenchymal morphogenesis.     

Requirement for Pak3 in Rac1-induced organization of actin and myosin during Drosophila larval wound healing

Rho-family small GTPases regulate epithelial cell sheet migration by organizing actin and myosin during wound healing. Here, we report that Pak3, but not Pak1, is a downstream target protein for Rac1 in wound closure of the Drosophila larval epidermis. Pak3-deficient larvae failed to close a wound hole and this defect was not rescued by Pak1 expression, indicating differential functions of the two proteins. Pak3 localized to the wound margin, which selectively required Rac1. Pak3-deficient larvae showed severe defects in actin-myosin organization at the wound margin and in submarginal cells, which was reminiscent of the phenotypes of Rac1-deficient larvae. These results suggest that Pak3 specifically mediates Rac1 signaling in organizing actin and myosin during Drosophila epidermal wound healing.     

No strings attached: new insights into epithelial morphogenesis

The dramatic ingression of tissue sheets that accompanies many morphogenetic processes, most notably gastrulation, has been largely attributed to contractile circum-apical actomyosin 'purse-strings' in the infolding cells. Recent studies, however, including one in BMC Biology, expose mechanisms that rely less on actomyosin contractility of purse-string bundles and more on dynamics in the global cortical actomyosin network of the cells. These studies illustrate how punctuated actomyosin contractions and flow of these networks can remodel both epithelial and planarly organized mesenchymal sheets.