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Fruit fly brain study confirms complexity of neurodevelopment

By Michael Purdy

For years, two schools of thought have dominated neurobiologists' theories about how early nerve cells develop specialties that allow the assembly of a mature brain.   One theory, comparable to the U.S. federal government, suggests that master regulators trigger the development of the same specialized traits in cells found across wide regions of the brain. The other theory, more comparable to a town council, attributes the development of specialized traits to interactions between many local factors.

In a new study of developing fruit fly brain cells, scientists at Washington University School of Medicine in St. Louis and Harvard University showed that both models are valid and active. Surprisingly, they both appear to operate within single developing nerve cells.   By learning more about the most basic mechanisms that regulate the creation of the brain, scientists hope one day to gain new insights into developmental disorders that damage it.

"The moral of our story is that we really have to consider individual cell properties and the complexity of the mechanisms that underlie these properties," says Paul Taghert, Ph.D., professor of anatomy and neurobiology at Washington University. "Our system in the fruit fly lets us look at these factors at the level of individual cells, but even at that level the harder you push, the more you uncover the complexity that underlies these developmental systems."   Specialization of nerve cells is essential to normal brain function. All neurons have certain properties in common — spherical cell bodies and extending cell branches, for example. But as scientists have focused more closely on individual nerve cells, many variations have emerged.

"Some cell types have arms that are just a simple extension with a few branches, but some of them have quite an elaborate branching pattern," Taghert says. "The individual chemistries of these different types of nerve cells — the substances known as neurotransmitters that they emit, for example — also vary tremendously."   Other variations include changes in the cell membrane's responsiveness to stimulation and in the periods of time when brain cells are quiet and active. Taghert estimates that the fly brain contains several hundred different subtypes of nerve cells and guesses that the human brain may contain thousands.

Through studies of a fruit fly brain area containing five specialized cell types, Taghert and colleagues showed that developmental factors could participate in the "town council" model of neurodevelopment. In this model, many different sets of regulatory compounds interact in a nerve cell's nucleus to switch specialized traits on and off. The traits that are turned on and off are determined by which combinations of development factors are present in the cell.   But scientists also found evidence that some of the same developmental factors they studied were producing a "federal government" model of neurodevelopment, uniformly dictating the creation of the same specialized traits in many different cells across a wide region of the brain regardless of their interaction with other developmental factors.

To follow up, Taghert plans studies focused on a single developmental factor.   "We want to understand that regulator's own individual program in terms of the pattern of genes that it regulates," he says.

Allan WD, Park D, St. Pierre SE, Taghert PH, Thor S. Regulators acting in combinatorial codes also act independently in single differentiating neurons. Neuron, vol. 45, 689-700.

Funding from the National Institutes of Health supported this research.