Inner glow. Transplanted motor neurons (green) spread out from the spinal cord of an embryonic chick.

A Recipe for Motor Neurons

Researchers have taken an important step closer to repairing broken neurons. A team has turned embryonic stem cells into nerve cells and transplanted them into the spinal cords of chicks, where they grew into motor neurons. The results show that given the right signals, stem cells can be turned into neurons of choice.

When you wiggle your toes, or move any other muscles, motor nerve cells in your spinal cord send commands to your muscles via long tentacles. These tentacles, called axons, can break when injured or diseased. So far, efforts to cure the resulting paralysis by regrowing the extensions have been unsuccessful in humans and have reduced paralysis in, but not cured, injured rats. Adult neurons are less adaptable than young neurons, however, and researchers have turned to embryonic stem (ES) cells--blank slates that can turn into any cell type in the body. By manipulating the molecules bathing ES cells, they hope to create progenitors that will turn into motor neurons when transplanted.

To do this, a team of researchers led by neuroscientist Thomas Jessell at Columbia University created a mouse strain that produced green fluorescent protein (GFP) only in certain motor neurons. They grew mouse embryos until they had 1000 cells. Then they doused them with retinoic acid, a compound that stimulates stem cells to become more like neuron progenitor cells. Next they added a dash of protein called sonic hedgehog, which steers them down the path to becoming spinal cord neurons. The team found that 20% to 30% of the embryonic cells transmogrified into glowing motor neuron progenitor cells, they report in the 9 August issue of Cell.

The team then separated out the GFP-containing progenitors and injected them into the spinal cord of embryonic chickens, where the transplanted cells would pick up growth signals. After 3 days, the green-colored neurons projected extensions from the spinal cord, which contacted muscles. This demonstrates that stem cells can be coaxed into motor neurons if treated the same way as in a growing animal. "Now, if we know what normal development requires, we can write out a recipe for making not only motor neurons, but [any neuron type]," says Jessell.

This "incredible paper" is a "huge step forward," says neurologist John McDonald at Washington University in St. Louis, Missouri. "It's a critical demonstration that ES-derived cells do the right thing, that they behave in a normal and appropriate way." Now that they know that, researchers can learn how to transplant the cells into older animals and, eventually, animals and people with real nerve injury.

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Jessell's lab at Columbia University