BUSCADOR RECOLECTA

Muscle development is a multistep process that involves cell specification, myoblast fusion, myotube migration, and attachment to the tendons. In spite of great efforts trying to understand the basis of these events, little is known about the molecular mechanisms underlying myotube migration. Knowledge of the few molecular cues that guide this migration comes mainly from studies in Drosophila. The migratory process of Drosophila embryonic muscles involves a first phase of migration, where muscle progenitors migrate relative to each other, and a second phase, where myotubes migrate searching for their future attachment sites. During this phase, myotubes form extensive filopodia at their ends oriented preferentially toward their attachment sites. This myotube migration and the subsequent muscle attachment establishment are regulated by cell adhesion receptors, such as the conserved proteoglycan Kon-tiki/Perdido. Laminins have been shown to regulate the migratory behavior of many cell populations, but their role in myotube migration remains largely unexplored. Here, we show that laminins, previously implicated in muscle attachment, are indeed required for muscle migration to tendon cells. Furthermore, we find that laminins genetically interact with kon-tiki/perdido to control both myotube migration and attachment. All together, our results uncover a new role for the interaction between laminins and Kon-tiki/Perdido during Drosophila myogenesis. The identification of new players and molecular interactions underlying myotube migration broadens our understanding of muscle development and disease., Peer reviewed

Muscle development is a multistep process that involves cell specification, myoblast fusion, myotube migration, and attachment to the tendons. In spite of great efforts trying to understand the basis of these events, little is known about the molecular mechanisms underlying myotube migration. Knowledge of the few molecular cues that guide this migration comes mainly from studies in Drosophila. The migratory process of Drosophila embryonic muscles involves a first phase of migration, where muscle progenitors migrate relative to each other, and a second phase, where myotubes migrate searching for their future attachment sites. During this phase, myotubes form extensive filopodia at their ends oriented preferentially toward their attachment sites. This myotube migration and the subsequent muscle attachment establishment are regulated by cell adhesion receptors, such as the conserved proteoglycan Kon-tiki/Perdido. Laminins have been shown to regulate the migratory behavior of many cell populations, but their role in myotube migration remains largely unexplored. Here, we show that laminins, previously implicated in muscle attachment, are indeed required for muscle migration to tendon cells. Furthermore, we find that laminins genetically interact with kon-tiki/perdido to control both myotube migration and attachment. All together, our results uncover a new role for the interaction between laminins and Kon-tiki/Perdido during Drosophila myogenesis. The identification of new players and molecular interactions underlying myotube migration broadens our understanding of muscle development and disease., Peer reviewed

Autonomous oscillatory dynamics are ubiquitous at every level in Biology. At the cellular level, one of the most relevant and well characterized examples of periodic behavior is the cyclic assembly and disassembly of actomyosin networks. In Drosophila, these oscillations induce the robust contraction and expansion of individual cells required for correct dorsal closure, while in the follicular epithelium that surrounds the germline, periodic contractions of the basal actomyosin network are required for proper elongation of the egg chamber. While some studies suggest that actomyosin oscillations are driven by upstream signaling or mechanochemical features, we have recently proposed that they arise as a systems property from the competition between two well characterized features of the actomyosin machinery: 1) cooperative assembly of actin networks mediated by Actin crosslinker proteins and 2) tension-induced disassembly of actin networks mediated by myosin motors. Here, we perform experiments in amnioserosa and in the follicle cells of drosophila and simulations using a coarse-grained model of the actomyosin cortex to characterize the properties of the oscillations and how they depend on different features of the system. We also compare model and experiments to study the dynamics of actomyosin flows and the effect of mechanical coupling between cells in the tissue. In conclusion, our model is a powerful tool to study key features of actomyosin oscillations, from the effect of the individual components to network properties and finally supra-cellular organization of the oscillations at the tissue level., Peer reviewed

Additional file 2 Figure S1. Percentage of G-Actin in filaments. Percentage of G-Actin in filaments of different size for the three characteristic regimes., Ministerio de Ciencia, Innovación y Universidades Ministerio de Ciencia, Innovación y Universidades, Peer reviewed

Additional file 5 Figure S3. G-Actin, F-actin after incorporation of ACs. Number of G-Actin in the grid (green), G-actin as part of networks (orange) and ACs (blue) after incorporation of ACs into the system at t=5E6 iterations. The formation of networks is initial very fast, followed by a regime where incorporation of molecules into networks is gradually slowing down until equilibrium is reached., Ministerio de Ciencia, Innovación y Universidades, Peer reviewed

Additional file 6: Movie S3. Time-lapse movie of the system showing oscillations. Time-lapse movie of the system showing periodic assembly and disassembly of the actomyosin cortex (G-actin labeled in green, ACs labeled in red, Myosin labeled in red)., Ministerio de Ciencia, Innovación y Universidades, Peer reviewed

Additional file 8: Movie S4. Oscillations in D. Melanogaster basal follicle cells. Control conditions. Cells are stained with Lifeact-GFP., Ministerio de Ciencia, Innovación y Universidades, Peer reviewed

Additional file 9: Movie S5. Oscillations in D. Melanogaster basal follicle cells. Experimental conditions. Time-lapse movie of the D. Melanogaster basal follicle cells stained with Lifeact-GFP in conditions of over-expression of the two subunits of the integrin molecule., Ministerio de Ciencia, Innovación y Universidades, Peer reviewed

Additional file 12 Figure S7. Scheme of the effect of Myosin over F-actin. (1), Myosin movement in parallel f-Actin. (2) F-actin sliding. (3) Tension building in the filaments. (4) Release from cortex after threshold tension is reached. After release, tension (illustrated in red) is redistributed to other F-actin in the network., Ministerio de Ciencia, Innovación y Universidades, Peer reviewed

Autonomous oscillatory dynamics are ubiquitous at every level in Biology. At the cellular level, one of the most relevant and well characterized examples of periodic behavior is the cyclic assembly and disassembly of actomyosin networks. In Drosophila, these oscillations induce the robust contraction and expansion of individual cells required for correct dorsal closure, while in the follicular epithelium that surrounds the germline, periodic contractions of the basal actomyosin network are required for proper elongation of the egg chamber. While some studies suggest that actomyosin oscillations are driven by upstream signaling or mechanochemical features, we have recently proposed that they arise as a systems property from the competition between two well characterized features of the actomyosin machinery: 1) cooperative assembly of actin networks mediated by Actin crosslinker proteins and 2) tension-induced disassembly of actin networks mediated by myosin motors. Here, we perform experiments in amnioserosa and in the follicle cells of drosophila and simulations using a coarse-grained model of the actomyosin cortex to characterize the properties of the oscillations and how they depend on different features of the system. We also compare model and experiments to study the dynamics of actomyosin flows and the effect of mechanical coupling between cells in the tissue. In conclusion, our model is a powerful tool to study key features of actomyosin oscillations, from the effect of the individual components to network properties and finally supra-cellular organization of the oscillations at the tissue level., Peer reviewed