Glia
GLIAL cells constitute 25 per cent of the brain of a fly, 65 per cent of that of a rat and 90 per cent of that of a human being. Yet, their functions have remained shrouded in mystery. F W Pfrieger and B A Barres Of USA'S Stanford University School of Medicine have recently surveyed a whole list of possible glial functions; the crucial question these scientists ask is whether it would matter if there were no glia (Cell, Vol 63, 1995).
The researchers addressing this question have selectively eliminated glial cells during the growth of the Drosophila (fruitfly) brain. They have identified a gene called gcm - which stands for glial cells missing - that functions in the developing glia and encodes a protein present in the cell nucleus. As with many other developmental genes that have been identified, gcm appears to function as an 'either- or' switch. A cell in which it is active becomes a glial cell and a cell (from the same general pathway) in which it is inactive becomes a neuron (in this case, the glial cell is 'missing', whence the name of the gene).
Besides gcm, there is another protein in Drosophila, REPO', that is restricted to glia. The central nervous system of Drosophila is segmented and each segment consists of about 200 neurons and 50 glial cells. It was presumed that in flies, as in mammals, glial cells form a scaffolding that enables growing neurons to determine the correct pathway to follow during growth. In gcm-mutant flies, neuronal outgrowths (called axons) extend in the correct direction to begin with, but show misroutings later. They also tend to unravel from their normal bundles and degenerate. This last bit suggests that glial cells may be needed for neuronal survival and differentiation too.
This was conclusively shown by examining what happens - in gcm- mutant flies - to a specific nerve cell called the bipolar dendrite (BD) neuron. This neuron is associated with a glial support cell. The gcm-mutant lacks the support cell; it turns out that the BD neuron also lacks the dendrites even though the cell body and axon appear normal. This points to the probability of glial cells being responsible for the formation of dendrites in neurons, or perhaps for their maintenance once they are formed.
Till date it was believed that all glial cell shapes were little more than developmental modifications of the same basic theme, expressions of the inherently plastic nature of glia. However, it is beginning to emerge that there may be as diverse an array of glial cells as of neurons. For example, neurons that overexpress gcm get transformed, not into just any kind of glia, but into typical BD glia. Conversely, in the gcm-mutant fly, the glial support cell starts to look, not like any neuron, but like the BD neuron.
While they are fascinating, these results leave unanswered a number of tantalising questions. For example: how does gcm protein perform its role? And is there any equivalent of gcm in humans, an equivalent that can enable scientists to investigate the role of glia in mammals?