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Abstract
When migrating in vivo, cells are exposed to numerous conflicting signals: chemokines, repellents, extracellular matrix, growth factors. The roles of several of these molecules have been studied individually in vitro or in vivo, but we have yet to understand how cells integrate them. To start addressing this question, we used the cephalic neural crest as a model system and looked at the roles of its best examples of positive and negative signals: stromal-cell derived factor 1 (Sdf1/Cxcl12) and class3-Semaphorins. Here we show that Sdf1 and Sema3A antagonistically control cell-matrix adhesion via opposite effects on Rac1 activity at the single cell level. Directional migration at the population level emerges as a result of global Semaphorin-dependent confinement and broad activation of adhesion by Sdf1 in the context of a biased Fibronectin distribution. These results indicate that uneven in vivo topology renders the need for precise distribution of secreted signals mostly dispensable.
Highlights
IntroductionCells are exposed to numerous conflicting signals: chemokines, repellents, extracellular matrix, growth factors
When migrating in vivo, cells are exposed to numerous conflicting signals: chemokines, repellents, extracellular matrix, growth factors
An ectopic source of Sdf[1] was sufficient to attract cells into Semaphorin-rich regions[19] and similar observations were made using VEGFA in chick[22]. These data suggest that attractants might not give directions but could contribute to the definition of what is a permissive environment for migration. These results raise the question of how cells integrate local signals in order to initiate directional migration and what could putative attractants such as Sdf[1] or VEGFA do in this context if their distributions are not restricted to target tissues
Summary
Cells are exposed to numerous conflicting signals: chemokines, repellents, extracellular matrix, growth factors. These results raise the question of how cells integrate local signals in order to initiate directional migration and what could putative attractants such as Sdf[1] or VEGFA do in this context if their distributions are not restricted to target tissues To address this question, we used the Xenopus cephalic NC cells as a model and focused on the most-studied positive and negative signals regulating NC migration: sdf[1] and class3Semaphorins[23]. Our results indicate that in the context of a non-homogenous environment (physical constraints, biased distribution of matrix), a direct competition between pro and anti-adhesion signals at the singlecell level can be efficiently translated into directional migration at the population level This strongly suggests that in environments with a clear topology, the structuration of putative attractants in large scale gradients is likely to be dispensable
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