Electrical zap of cells shapes growing brains

A little electricity goes a long way in shaping the growing brain. The electric charge across cell membranes directs many aspects of brain development, scientists report March 11 in the Journal of Neuroscience. Harnessing these charges could eventually allow scientists to fix birth defects or grow new tissue.

The researchers tinkered with the voltage in cell membranes of developing African clawed frogs (Xenopus laevis)and found that electric charge plays a role in how big the brain grows and what kind of tissue developing cells grow into. Changing voltage, also called membrane potential, even fixed a brain-damaging birth defect.

The new research “highlights the importance of membrane potential and its role in development,” says Simon Perathoner, a developmental biologist at the Max Planck Institute for Developmental Biology in Tübingen, Germany.

All cells have electrical activity in their membranes. “Cells use this electrical activity to communicate with each other in making decisions about growth,” says study coauthor Michael Levin, a developmental biologist at Tufts University in Medford, Mass. “For the first time here, we also show that these bioelectrical signals are used to determine the size and location of the brain itself.” For instance, changing voltage can make brain tissue grow in a tadpole embryo’s tail.

Levin and his colleagues stained developing embryos with dyes that glow less or more intensely depending on variations in electric charge in cell membranes. The researchers then flipped genes that control cell growth on or off by inducing the growth of tiny structures called ion channels in cell membranes.  

“We put [ion channels] into cells as needed to move the voltage up or down,” says Levin. “We were able to make the brain cells grow more, or less, as we wanted, thus showing that voltage controls the size of the primary brain.”

Changing the voltage in cell membranes also led to brain tissue growing outside of the brain area in the frog embryos. “It switched the fate of other cell types into that of brain,” says Levin.

The brain tissue in other parts of the body provides evidence that cells rely on bioelectric cues to decide what type of tissue they should grow into, and that these cues can prompt new brain tissue to grow.

Regenerative medicine could take advantage of cells’ reliance on bioelectricity to grow new tissue to replace missing or damaged organs, Levin says.

The team also manipulated errant brain voltage in frog embryos with a genetic mutation that leads to much of the brain being malformed or missing. When the researchers restored the voltage in brain cell membranes, the embryos developed nearly normal brains.

Many drugs already exist to tweak ion channels, says Levin. The team’s success in fixing a genetic defect with bioelectricity indicates that ion channel drugs could treat birth defects or degenerative brain disease.