More MS news articles for Nov 2001

Glial cells build the brain

Sunday Nov 11th, 2001
Investigator: Magdalena Götz
by Roberta Friedman

Research presented here is beginning to reveal the molecular signals that guide the assembly of the brain, and that perhaps can be tapped into for making repairs. The glial cells that most neuroscientists have regarded as merely support cells in fact take an active role in building a brain. A primitive type of glial cell serves as the stem cells that actually generate the brain's neurons. Even in adults, these glial cells can form new neurons, scientists are finding.

Evidence presented in a symposium supports the idea that the radial glial cells are actually the stem cells that give rise to neurons, and are not just directing their migration passively. Magdalena Götz and colleagues at the Max-Plank Institute of Neurobiology find that a transcription factor, Pax6, is used in the radial glial cells that are forming neurons.

Only certain brain regions have radial glial cells that contain the Pax6 protein, and in those regions, such as the cerebral cortex, these glial cells give rise to neurons. These are the same neurons that neuroanatomists have found migrating up the long arm of the radial glial cell, to arrive at their cortical destination.

Pax6 appears to be specific for certain regions of the brain. Other brain locations, such as the area that gives rise to the basal ganglia, do not have Pax6 in their radial glia. "Pax6 drives the neurogenic radial glia," Götz says, adding that it is "necessary and sufficient" to instruct these glial cells to make neurons.

Fluorescence-activated cell-sorting experiments, using glial cells labelled by green fluorescent protein, confirm that the radial glial cells generate most of the new neurons, according to work presented by Stephen Noctor's team at Columbia University.

Confocal microscopy, meanwhile, allows researchers at the University of California-San Francisco to follow the process as the radial glial cell extends a cellular arm from its place at the base of the cortex, by the cerebral ventricle, up to the cortical surface. The glial cell then divides to generate a daughter cell, which migrates up the radial arm.

The technique "shows how cells end up in a specific place," neuroanatomist Pasko Rakic of Yale University told BioMedNet News. "You don't have to infer" with this technique, he went on. "You see it." Today's molecular biology, Rakic says, is able to confirm what the earliest studies of the cellular architecture of the brain had only been able to suggest. Rakic is certain that the neurogenic process described at the meeting is not limited to animals. "I would put my money," he said, "this is true in humans."

The radial glial cell is no longer considered to be playing a "bit part" in building the brain, says Gordon Fishell of New York University Medical Center, who finds that Notch and FGF are other important molecular factors involved in the glial cell's role. Ultimately, isolating the molecular signals that guide the radial glial cell in its genesis of the brain's structure could lead to the ability to make adult glial cells neurogenic again, and thereby repair brain damage, Götz says.

"This would give hope to put back molecules to activate" the glial cells, Götz said, adding that "unfortunately, these experiments aren't as fast as we were hoping."

SFN 2001 - Society for Neuroscience

Editor's Choice Links

Neurons derived from radial glial cells establish radial units in neocortex.
Noctor SCFlint ACWeissman TADammerman RSKriegstein AR
Nature 2001 Feb 8 409:6821 714-20

A unified hypothesis on the lineage of neural stem cells.
Alvarez_Buylla AGarcia_Verdugo JMTramontin AD
Nat Rev Neurosci 2001 Apr 2:4 287-93

Characterization of CNS precursor subtypes and radial glia.
Hartfuss EGalli RHeins NGotz M
Dev Biol 2001 Jan 1 229:1 15-30

Telencephalic neural progenitors appear to be restricted to regional and glial fates before the onset of neurogenesis.
McCarthy MTurnbull DHWalsh CAFishell G
J Neurosci 2001 Sep 1 21:17 6772-81

See also:

Neuronal potential and lineage determination by neural stem cells [Review]
Sean J. Morrison
Current Opinion in Cell Biology, 2001, 13:6:666-672

Neural stem cells [Review]
Jack Price and Brenda P. Williams
Current Opinion in Neurobiology, 2001, 11:5:564-567

A new 'spin' on neural stem cells? [Review]
Cindi M Morshead and Derek van der Kooy
Current Opinion in Neurobiology, 2001, 11:1:59-65

© Elsevier Science Limited 2000