During development, a cell needs to know up from down and left from right. For example, a disoriented hair follicle could produce hair growing into, rather than out of, the body. HHMI Investigator Roel Nusse has shown that a localized source of a signaling molecule called Wnt3a coordinates orientation in a dividing stem cell.
Wnt proteins play key roles in embryonic development, tissue regeneration, bone growth, and stem cell differentiation. In the body, Wnt typically acts on receptors on just one portion of the cell. To recreate this “orientation effect” in the lab, Shukry Habib, a postdoctoral researcher in Nusse’s Stanford University lab, attached Wnt protein to tiny beads and added the beads to dishes of growing embryonic stem cells. Habib then used a Bessel beam plane illumination microscope—a high-speed, high-resolution, three-dimensional imaging device created by Janelia Lab Head Eric Betzig—to watch the cells respond to the beads.
|When grown with a Wnt3a-coated bead (blue), embryonic stem cells divide such that one daughter cell is proximal to the Wnt3a signal, and the other daughter cell is distal to the signal. Segregating chromosomes of the dividing cell are seen in orange.|
The effects of the localized signal were clear, according to the team’s March 22, 2013, report in Science. The stem cells all divided in the same way, with the plane of division occurring perpendicular to the location of the incoming Wnt signal. Furthermore, the daughter cell closest to the bead retained the characteristics of an embryonic stem cell while the more distant progeny cell began to differentiate into a specialized cell. “That makes sense,” Nusse says, “because the Wnt signal is important for stem cell fate, and the lack of a Wnt signal would allow the distal cell to differentiate.”
Next, Nusse and his team will try to uncover the molecules that help Wnt orient cell division.