Biochemical and biophysical mechanisms of multicellular organization

8 May 2015

Jennifer Zallen
Developmental Biology Program
Memorial Sloan Kettering Cancer Center


A major challenge in developmental biology is to understand how tissue-scale changes in organism structure arise from events that occur on a cellular and molecular level. In Drosophila, the characteristic elongated head-to-tail body axis is achieved through rapid and coordinated movements of hundreds of cells. We found that these movements are regulated by subcellular asymmetries in the localization of the machinery that generates contractile and adhesive forces between cells. We have identified a positional spatial code that systematically orients cell movements throughout the embryo and demonstrate that this spatial information is provided by an ancient family of Toll-related receptors that are widely used for pathogen recognition by the innate immune system. Using live imaging combined with tools for automated image analysis, we showed that these spatial cues drive collective behaviors in which groups of cells assemble into higher-order rosette structures that form and resolve directionally, promoting efficient elongation. Rosettes form through a force-based mechanism in which an initial asymmetry in actomyosin contractility is amplified by mechanical tension, triggering the formation of supracellular contractile networks that promote efficient elongation. Polarized actomyosin contractility and rosette behaviors have now been shown to drive convergent extension in flies, chicks, and mice, and represent a general mechanism linking cellular asymmetry to global tissue reorganization. We are currently using cell biological, biophysical, and quantitative imaging approaches to understand how genes encode the forces that shape tissues, and to elucidate the mechanotransduction mechanisms that allow cells to modulate their behavior in response to changes in their mechanical environment.

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