The researchers made this discovery when they compared the development of normal antennal lobes to those that formed when Wnt5 or derailed were missing, present at very low levels, or present at extremely high levels.
When Wnt5 was absent, the normally symmetrical odor-sensing structures, called glomeruli, were smaller, malformed, and grew in lopsided positions in the antennal lobes. The commissure, a network of neural fibers that connects the lobes, also was missing.
Because receptors and their ligands normally work together, the researchers expected to see the same problems in the mutant that lacked the derailed receptor. But in these mutants they observed a new phenomenon: Not only were the glomeruli misplaced, they were also growing in the commissure, where they had never been seen before.
This is when we realized something weird was going on, Hing said.
This growth of glomeruli in the commissure also occurred when Wnt5 was present at extremely high levels. These observations indicated that the derailed receptors were somehow keeping the Wnt5 protein in check. When derailed was absent Wnt5 was moving into regions where it didnt belong, and the neural fibers that formed the glomeruli were following. Neural development was truly derailed.
Further studies determined that supporting cells not the neurons themselves were expressing the derailed receptor.
The study reveals an unusual mechanism that is important to the development of the olfactory system, and perhaps to other parts of the nervous system, Hing said. But it also will interest cancer researchers, he said, because the genes that code for the Wnt class of proteins are oncogenes, which sometimes induce the growth of cancer cells.
Perhaps one day down the road we can make pharmaceutical agents that imitate the role of the derailed receptor, Hing said.
|Contact: Diana Yates|
University of Illinois at Urbana-Champaign