Zallen’s lab group recently combined molecular techniques with Drosophila genetics to characterize one facet of that junctional regulation. In work published February 14, 2012, in Developmental Cell, they identified a biochemical cue that allows cells to disengage from some neighbors in a rosette so they can find new ones. They found that a signaling factor, the tyrosine kinase protein Abl, makes the contact points (known as adherens junctions) between cells in a rosette more dynamic or fluid—in other words, it allows cells to glide more smoothly against one another. Fruit fly embryos genetically engineered to lack Abl show poor rosette formation and impaired elongation. Surprisingly, the more dynamic junctions in normal embryos are also stronger, resisting apparent breaks or tears seen in embryos lacking Abl.

Equally essential for axis formation are mechanical signals that rope cells into a rosette. In work published in Developmental Cell in 2009, Zallen reported that cells perceive physical tension exerted by their neighbors. These mechanical signals promote rosette cohesion by prompting the motor protein myosin to join long cables that extend across multiple cells and contract like a drawstring, pulling cells together to form a rosette.

One way her group showed this experimentally was by literally tugging on a Drosophila embryo with a glass needle and then using live imaging to watch as fluorescently labeled myosin was recruited to the needle. This experiment helped explain one purpose that mechanical forces serve, namely, to bring cells together into multicellular gatherings.

Whether the same mechanisms that push and pull cells in a simple organism like Drosophila drive convergent extension in vertebrate embryos remains unknown. “Right now, people have seen snapshots of something that looks like rosettes in other animals,” she says, noting that the vertebrate neural tube (the embryonic structure that gives rise to the central nervous system) exhibits pinwheel-like swirls of cells. “But rosette formation is a dynamic behavior that is difficult to assess in a static picture. Live imaging of vertebrate cells is needed to see if these cells move in a way that leads to elongation.”

Even if she and others discover that vertebrates evolved a different way to form tubular organs, Zallen has an ambitious long-term goal: to figure out how large populations of cells act collectively. “Over the past 20 years, people have learned a lot about factors that determine cell identity,” she says. “But we know much less about how cells get to the right place to build a three-dimensional animal. This is the big unsolved question in developmental biology.”

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