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Astrocytes play starring role in neural stem cell development

Stevens said that at first it seemed likely that the astrocytes might be keeping the stem cells alive longer or encouraging proliferation. In other words, they might be merely supporting the cells in becoming functional neurons, Stevens said.

"Another possibility was that the astrocytes were somehow actually instructing the stem cells to divide and adopt a neuronal fate," he said. "This seemed least likely because when the embryonic brain is growing, most of the neurons are born before the glia, so one wouldn't have thought glia were instructing stem cells."

To define the astrocytes contribution to neuronal development, Song, Stevens and Gage tagged adult neural stem cells with a green fluorescent marker so they could follow the development of those cells. When they grew the tagged stem cells in cell culture with both astrocytes and other neurons, the stem cells readily developed into mature neurons. However, when the scientists grew the tagged stem cells in cultures enriched with astrocytes, they found that the astrocytes supported the growth of many more neurons from the stem cells.

A big question, said Stevens, was whether the astrocytes influenced neuronal growth by releasing chemicals or by direct contact with the stem cells. So, the scientists cultured neural stem cells so that they could not touch the astrocytes, or so that the astrocytes were gently killed and could not release regulatory chemicals. The experiments showed that in both cases, the astrocytes triggered stem cell development. This suggests that astrocytes trigger neuronal growth both by releasing chemicals and through a contact-related signal, Stevens said.

Mathematical analysis of the cells in culture revealed that astrocytes encouraged both stem cell proliferation and their maturation into neurons. "We found that stem cells grown on glia divided about twice as fast as they did when grown on fibroblasts," said Stevens. "Glia make a good environment to instru
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
3-May-2002


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