Glial cells help shape brain

Glia and neurons collaborate to degrade unwanted axons during brain development

Apr 22, 2004
Helen Dell(helen.dell@absw.org.uk)

Glial cells, whose function is poorly understood, seem to cooperate actively with neurons to sculpt neural circuits in the developing brain, according to two studies published in the April 20 Current Biology.

During development, the controlled and programmed death of specific cells is as important as the survival of others; for example, the webbing on embryonic hands degenerates to fashion fingers from a clump of tissue, according to V. Hugh Perry, professor of experimental neuropathology at the University of Southampton, who was not involved in the studies. The brain is no exception. Brain development involves the production of excess neurons and axonal branches, which then die back in a process dubbed “pruning.”

Both papers study the remodeling of neural networks that occurs during the metamorphosis of Drosophila, where unwanted larval axons degrade to form adult neurons. The first paper, from Liqun Luo's lab at Stanford University, is “a particularly beautiful ultrastructural study,” according to an accompanying commentary by Kendal Broadie, of the Department of Biological Science at Vanderbilt University. The second paper, from Takeshi Awasaki and Kei Ito at the University of Tokyo, provides experimental evidence of the importance of glia in the pruning process.

Luo and colleagues used a genetically encoded marker to highlight different cell types—neurons or glia—so they could watch the pruning process using electron microscopy. They observed that during pruning, glia invade the surrounding area and absorb the degenerating axons. They also found evidence that the glia might have an active role in the process, rather than just cleaning up after axonal breakdown, as some features of the glial invasion happen independently of the axonal degeneration.

Awasaki and Ito adopted a different methodology, first examining the morphology of the axon branches during pruning. They observed hole-like structures among the branches and suggest that each “hole” corresponds to a clump of glia infiltrating from outside the bundle.

“This finding was very unexpected and was a breakthrough of this study,” said Awasaki. Inhibiting cellular functions in the glia also inhibited glial infiltration into the axonal bundles and suppressed axonal pruning, suggesting that the glia actively break down axons rather than just scavenge debris.

“Taken together, these papers suggest that glia definitely play an active role in engulfing the [axonal] fragments,” Luo told The Scientist. However, whether the glia are actually regulating the process remains to be seen, he said.

“As yet, we just don't have a biology of synapse and axon degeneration,” said Perry. “So this is a very interesting subject.”

“These new papers are the first to report experimental evidence for the importance of neuron–glia interaction, and the indispensable role of glia during developmentally regulated axon pruning,” wrote Broadie.

“The molecules required for the communication between degenerating axons and phagocytosing glia will be the next big prize,” Broadie concluded