Watching the Cellular Clock

A new way to visualize single-cell activity in living zebrafish embryos has allowed scientists to clarify how cells line up in the right place at the right time to receive signals about the next phase of their life.

Scientists developed the imaging tool in single living cells by fusing a protein defining the cells’ cyclical behavior to a yellow fluorescent protein that allows for visualization. Zebrafish embryos are already transparent, but with this closer microscopic look at the earliest stages of life, the researchers have answered two long-standing questions about how cells cooperate to form embryonic segments that later become muscle and vertebrae.

Though these scientists are looking at the molecular “clock” that defines the timing of embryonic segmentation, the findings increase understanding of cyclical behaviors in all types of cells at many developmental stages – including problem cells that cause cancer and other diseases. Understanding how to manipulate these clocks or the signals that control them could lead to new ways to treat certain human conditions, researchers say.

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Under normal circumstances in zebrafish embryos, cells oscillate in synchrony with their neighbors as they prepare to make segments that later become muscle and vertebrae. When a color map (top left corner) is used to indicate the phase of oscillation in each cell at any fixed snapshot of time, with cool colors representing the peak of the gene activation wave and warm colors the lower levels of activation, it is evident in the top image that neighboring cells are in a similar phase, or transitioning smoothly to the next phase. However, in embryos lacking a powerful messaging system called Notch signaling, that synchrony is lost. In the bottom map, cells in mutant embryos that lack the Notch signal are oscillating, but the random assortment of colors without smooth transitions shows that Notch is required to synchronize the oscillations in neighboring cells. Images courtesy of Ohio State University

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