Embryonic stem cells have shown a great deal of promise for alleviating heart disease and regenerating organs. But for some of the conditions for which people hold out the most hope - Alzheimer's and Parkinson's, for example - there's been little evidence to date that stem cells can work.
Part of the problem is that neural stem cells, especially those involved in brain development, specialize as they mature and lose their ability to diversify. They require very specific environmental cues in a very specific order, and scientists have so far been unable to prod them to go through each of the necessary steps. But now, for the first time, a new study in mice shows that embryonic
The cerebellum, which is tucked into the lower, rear portion of the mammalian brain, contains neural circuits that are responsible for motor learning, motor memory and sensory perception. It's also the location of 40 percent of pediatric brain tumors. Mary E. Hatten, Rockefeller's Frederick P. Rose Professor and head of the Laboratory of Developmental Neurobiology, has been studying granule cells for 30 years; she sees her results as a step toward understanding how embryonic stem cells could be regulated in vivo and ultimately used for cell replacement therapy, especially after childhood tumors, in the central nervous system.
Hatten and postdoc Enrique Salero found that in order to get the embryonic stem cells to differentiate, progressing through each of the known steps of granule neuron maturation as they did so, the cells had to be treated with signals that induce specific transcription factors - proteins that can turn genes on and off - in a specific order. The researchers then implanted the newly differentiated cells into a specific spot in the brains of newborn mice, the gray layer on the surface of the cerebellum called the cerebellar cortex. Once in the brain, the cells extended parallel fibers, migrated to and incorporated themselves into the internal granule cell layer, and extended short projections called dendrites, something that neurons use to communicate with each other. Each of these steps, Hatten says, is characteristic of a typical granule cell.