Closing in on Mechanisms of Tissue Morphogenesis
2009; Cell Press; Volume: 137; Issue: 7 Linguagem: Inglês
10.1016/j.cell.2009.06.009
ISSN1097-4172
Autores Tópico(s)Microtubule and mitosis dynamics
ResumoIt remains largely unknown how large-scale tissue movements during development emerge from the interplay of different tensile forces associated with actomyosin networks. Solon et al., 2009Solon J. Kaya A. Colombelli J. Brunner D. Cell. 2009; (this issue)PubMed Google Scholar now report that a ratchet-like mechanism drives the movement of epithelial sheets during dorsal closure in embryos of the fruit fly Drosophila. It remains largely unknown how large-scale tissue movements during development emerge from the interplay of different tensile forces associated with actomyosin networks. Solon et al., 2009Solon J. Kaya A. Colombelli J. Brunner D. Cell. 2009; (this issue)PubMed Google Scholar now report that a ratchet-like mechanism drives the movement of epithelial sheets during dorsal closure in embryos of the fruit fly Drosophila. During development, epithelial tissues are extensively remodeled while maintaining their polarized architecture. A well-studied example is dorsal closure in embryos of the fruit fly Drosophila. During dorsal closure the lateral ectoderm migrates as a sheet toward the dorsal midline (Figure 1). Cells at the leading edge accumulate high levels of actin and myosin II at their front, forming a supracellular actin cable that contracts to produce “purse-string” tension. Simultaneously, the underlying dorsal squamous epithelium called amnioserosa contracts and pulls the lateral ectoderm (Hutson et al., 2003Hutson M.S. Tokutake Y. Chang M.S. Bloor J.W. Venakides S. Kiehart D.P. Edwards G.S. Science. 2003; 300: 145-149Crossref PubMed Scopus (373) Google Scholar). Solon et al., 2009Solon J. Kaya A. Colombelli J. Brunner D. Cell. 2009; (this issue)PubMed Google Scholar now shed new light on how these two steps are coordinated. They show that pulsed contractile forces produced by amnioserosa cells are stabilized by epidermal actin cables to drive the movement of the epithelial sheet during dorsal closure in a ratchet-like mechanism. Tissue remodeling relies on changes in cell shape as a result of forces generated by actomyosin cytoskeletal networks and the transmission of these forces at the cell cortex by adhesion molecules (Lecuit and Lenne, 2007Lecuit T. Lenne P.F. Nat. Rev. Mol. Cell Biol. 2007; 8: 633-644Crossref PubMed Scopus (788) Google Scholar). For instance, myosin II-based tension drives polarized remodeling of junctions and tissue elongation in fly embryos (Bertet et al., 2004Bertet C. Sulak L. Lecuit T. Nature. 2004; 429: 667-671Crossref PubMed Scopus (637) Google Scholar, Blankenship et al., 2006Blankenship J.T. Backovic S.T. Sanny J.S. Weitz O. Zallen J.A. Dev. Cell. 2006; 11: 459-470Abstract Full Text Full Text PDF PubMed Scopus (451) Google Scholar, Rauzi et al., 2008Rauzi M. Verant P. Lecuit T. Lenne P.F. Nat. Cell Biol. 2008; 10: 1401-1410Crossref PubMed Scopus (399) Google Scholar), and myosin II accumulation drives apical constriction during fly mesoderm invagination (Martin et al., 2009Martin A.C. Kaschube M. Wieschaus E.F. Nature. 2009; 457: 495-499Crossref PubMed Scopus (742) Google Scholar) and vertebrate neural tube closure (Hildebrand, 2005Hildebrand J.D. J. Cell Sci. 2005; 118: 5191-5203Crossref PubMed Scopus (189) Google Scholar). Although the mechanical elements that underlie tissue morphogenesis are better understood at the level of single cells, recent analyses have begun to yield insights into their dynamics in whole tissues. This includes detailed measurements of cell deformations in dorsal closure (Gorfinkiel et al., 2009Gorfinkiel N. Blanchard G.B. Adams R.J. Martinez Arias A. Development. 2009; 136: 1889-1898Crossref PubMed Scopus (113) Google Scholar). Now, Solon et al. extend this and examine the temporal dynamics of cell movements during dorsal closure. They find that the apical surface exhibits a pulsed behavior with alternating phases of contraction and relaxation. Strikingly, the pulses are not random fluctuations but instead tend to follow a regular temporal pattern. Moreover, the pulses are spatially regulated, starting in amnioserosa cells that contact cells at the leading edge of the epidermis and then spread dorsally. This observation prompts the question of whether the pulses of amnioserosa cell contraction are coordinated. The authors report an anti-phase correlation between neighboring cells and an in-phase correlation between more distant cells. The coupling between cells is then probed by laser ablation: after disrupting a cell contact between two adjacent amnioserosa cells, surrounding cells stop pulsing. This is consistent with the notion that contracting cells may be mechanically coupled and that their activity is coordinated. This behavior may be a consequence of all cells attempting to contract together but failing to do so because of constraints imposed by synchronized constriction. A potentially similar phenomenon has been observed in vitro in Madin-Darby canine kidney cells expressing the actin-binding protein Shroom, which is required for apical cell constriction (Hildebrand, 2005Hildebrand J.D. J. Cell Sci. 2005; 118: 5191-5203Crossref PubMed Scopus (189) Google Scholar). Addressing the mechanisms of mechanical coupling between cells will be an important avenue to pursue in future work. Given the central role of amnioserosa contraction in dorsal closure, the authors address whether pulses of apical constriction are linked with the mechanics of dorsal closure. By tracking the position of the leading edge the authors make the key observation that it oscillates along the dorsal/ventral axis and that its movement correlates with the contraction/relaxation phases of amnioserosa cells. This suggests that the amnioserosa may cause leading edge oscillations. It turns out that there are two phases characterizing the dynamics at the leading edge: at first, the leading edge oscillates with no net dorsal displacement; later, the oscillations at the leading edge are associated with persistent motion toward the dorsal side. Superficially this would disqualify pulsed contractions of amnioserosa cells as an active element sufficient for dorsal closure. Solon et al. thus looked for a second player responsible for leading edge displacement during the second phase. A candidate is the actin cable in cells of the leading edge, which lines the circumference of the epidermal opening and is essential for dorsal closure (Franke et al., 2005Franke J.D. Montague R.A. Kiehart D.P. Curr. Biol. 2005; 15: 2208-2221Abstract Full Text Full Text PDF PubMed Scopus (202) Google Scholar). The authors observe that levels of F-actin in the actin cable increase steadily during closure, along with the straightening of the leading edge. These data support the notion that the actin cable is a contractile supracellular network, as has been reported previously (Franke et al., 2005Franke J.D. Montague R.A. Kiehart D.P. Curr. Biol. 2005; 15: 2208-2221Abstract Full Text Full Text PDF PubMed Scopus (202) Google Scholar, Hutson et al., 2003Hutson M.S. Tokutake Y. Chang M.S. Bloor J.W. Venakides S. Kiehart D.P. Edwards G.S. Science. 2003; 300: 145-149Crossref PubMed Scopus (373) Google Scholar). This prompted the authors to test whether there is mechanical coordination between the two force generators, actin cable contractility and amnioserosa contractions, during closure. Correlation analysis between amnioserosa movement and leading edge dynamics indicates that forces contributed by distinct components of the system may be mechanically coupled (Gorfinkiel et al., 2009Gorfinkiel N. Blanchard G.B. Adams R.J. Martinez Arias A. Development. 2009; 136: 1889-1898Crossref PubMed Scopus (113) Google Scholar). Solon and colleagues push this notion a bit further, documenting that the pulses of amnioserosa cells are dampened over time, which correlates with actin cable formation. In conditions that abrogate formation of actin cables (namely mutants that inactivate Jun kinase signaling) amnioserosa pulses are not dampened. This suggests that actin cable contraction may provide mechanical feedback on amnioserosa contractility, as pointed out by Gorfinkiel et al., 2009Gorfinkiel N. Blanchard G.B. Adams R.J. Martinez Arias A. Development. 2009; 136: 1889-1898Crossref PubMed Scopus (113) Google Scholar. The most important conceptual advance by Solon et al. is the proposal that the actin cable might stabilize transient dorsal displacement of the leading edge imposed by the contraction phases of amnioserosa cells. Indeed, before formation of the actin cable, or when the actin cable is disrupted, amnioserosa cell contractility is not accompanied by persistent dorsal-ward movement of the lateral epidermis. This suggests a ratchet mechanism: pulsed contractility of the amnioserosa causes transient dorsal displacement of the leading edge, which is prevented from relaxing ventrally by continuous contractility of the actin cable. Thus, when contractility of the actin cable and amnioserosa are combined, the leading edge moves in a ratchet-like manner. It is probable that this mechanism relies on specific adhesion between the leading edge and the amnioserosa. To some extent this is dependent on integrins and indeed integrin mutants have defects in dorsal closure (Hutson et al., 2003Hutson M.S. Tokutake Y. Chang M.S. Bloor J.W. Venakides S. Kiehart D.P. Edwards G.S. Science. 2003; 300: 145-149Crossref PubMed Scopus (373) Google Scholar). However, the role of integrins in this process has yet to be addressed. The data of Solon et al. build up to a computational model of dorsal closure, in which tension-dependent contraction force, a time delay (setting the oscillation periodicity), and a Hill coefficient (defining the sensitivity of a system in response to external stimuli) are varied to explore phase-pulsing transitions in silico. The simulations match the observed dynamics of dorsal closure and reinforce the plausibility of the model. This model bears similarities with one recently proposed for mesoderm invagination in which pulses of apical cell constriction are in synch with pulses of actomyosin accumulation within the same cells (Martin et al., 2009Martin A.C. Kaschube M. Wieschaus E.F. Nature. 2009; 457: 495-499Crossref PubMed Scopus (742) Google Scholar). Pulses of actomyosin contraction are followed by a phase of stabilization, suggesting that myosin II tension acts like a ratchet to drive constriction. Both Martin et al. and Solon et al. vividly illustrate how tissue level displacement emerges from the local interplay between contractility and stabilization in actomyosin tensile networks. Future studies will have to meet the challenge of understanding how this interplay is controlled at the molecular level. Pulsed Forces Timed by a Ratchet-like Mechanism Drive Directed Tissue Movement during Dorsal ClosureSolon et al.CellJune 26, 2009In BriefDorsal closure is a tissue-modeling process in the developing Drosophila embryo during which an epidermal opening is closed. It begins with the appearance of a supracellular actin cable that surrounds the opening and provides a contractile force. Amnioserosa cells that fill the opening produce an additional critical force pulling on the surrounding epidermal tissue. We show that this force is not gradual but pulsed and occurs long before dorsal closure starts. Quantitative analysis, combined with laser cutting experiments and simulations, reveals that tension-based dynamics and cell coupling control the force pulses. Full-Text PDF Open Archive
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