Meeting Abstract
S3.1-3 Saturday, Jan. 4 09:00 Shaping the embryo: Cellular dynamics in development ZALLEN, J.; HHMI and Sloan-Kettering Institute zallenj@mskcc.org
A major challenge in biology is to understand how large-scale changes in tissue structure are generated on a cellular and molecular level. In the fruit fly Drosophila, the characteristic elongated shape of the head-to-tail axis is achieved through the rapid and coordinated movements of hundreds of cells. We found that these movements are oriented by cellular asymmetries in the localization of the molecular machinery that generates contractile and adhesive forces between cells. Using quantitative imaging, we show that these asymmetries result in higher-order collective cell behaviors in which groups of cells assemble into multicellular rosette structures that form and resolve directionally, promoting efficient elongation. Rosettes form through a combination of biochemical and mechanical signals that spatially orient actomyosin contractile activity. An initial asymmetry in the localization of the myosin II motor protein is amplified by mechanical tension, promoting the formation of multicellular contractile networks that contract to promote efficient elongation. In addition, the dynamics of cell adhesion proteins are controlled by the spatially regulated activation of tyrosine kinase signaling at cell-cell junctions that are selectively targeted for disassembly, demonstrating an essential role for spatially regulated tyrosine kinase signaling in dynamic cell interactions during development. Multicellular rosette behaviors have since been shown to occur during epithelial elongation in vertebrates and may represent a general mechanism linking cellular asymmetry to tissue elongation. We are currently using molecular genetic and live imaging approaches to understand how genes encode the forces that generate polarized cell behavior, and developing biophysical methods to elucidate the mechanotransduction mechanisms that allow cells to modify their behavior in response to their mechanical environment.
