Binding Proteins Shown To Play Key Role In Early Brain Development

It has long been accepted that integrin is a must-have family of binding proteins for cell adhesion, migration and wound healing, and its presence in the brain and central nervous system is widely recognized. However, its necessity in the early stages of brain development had only been theorized and studied in test tubes -- with interesting but mixed results -- until now.

A University of Illinois study using embryos of live Drosophila, a fly with similar but less complex brain structures than those of vertebrates, indicates that without key integrin subunits, axons misfire and route randomly. The flies' guidance system is without an interpreter.

"When we put normal integrin proteins back into the brains of developing knockout flies [those genetically engineered without integrin], then the nervous system, almost like wildfire, was rescued and developed normally, despite the fact that other tissues down the line were still lacking integrin," said neuroscientist Akira Chiba, a professor of cell and structural biology and affiliate of the U. of I. Beckman Institute for Advanced Science and Technology.

The findings were reported in the Oct. 1 issue of the Journal of Neuroscience by Chiba and Bao Hoang, a doctoral student in cell and structural biology. The research, which involved the use of immunocytochemistry -- the study of cells using immunologic methods such as fluorescent antibodies -- was funded by the National Institutes of Health and the National Science Foundation.

Chiba and Hoang focused on individual linking units, or neurons, and the genetic activity that tells the early developing neuron process known as the axon where to go. "Our lab is interested in the genetic programs for brain development, especially making the connection from what is encoded in DNA to the brain's emergence," Chiba said.

"The axon is capable of communicating with the outside world," Chiba said. "It can collect information about its microenvironment. But the axon also has to interpret its cue and correctly activate certain molecular interpreters that will lead to local molecular reorganization, especially the cytoskeletal system. Every movement of the axon requires reorganization of the cytoskeleton."

In essence, Chiba said, it appears that specific molecules of integrin are vital to the initial wiring of the brain. "The axon will continue to grow without integrin, but it fails to interpret the cues that tell it when to stop or turn in a certain direction. It grows without direction.

"A lot of scientists have identified specific guidance cues of cells, which act much like traffic signals," he said. "We propose that integrin is one of the most, if not the most, key molecules that neurons use for interpreting traffic signals that guide them in their initial development."