Growth hormone found to have new role in development of brain's smell center

Compared to the visual system, the brain's odor system is still poorly understood, but it appears to have its own uniquely ordered connections, Ngai said. The nose contains some 5 million nerve cells, each of which carries only one kind of odor receptor out of about 1,000 different odor receptors, each tuned to detect different chemicals or odorants. Nose nerve cells that detect the same odorant send their axons to the same region of the olfactory bulb, and it appears that neurons that detect similar chemicals, such as different alcohols, send their axons to nearby areas of the bulb.

Scientists previously had discovered that each of our two olfactory bulbs is divided down the middle between two mirror-image representations of the nasal odor receptors. Ngai and his colleagues found that IGF is responsible for setting up these mirror images within the bulb.

"IGF signaling is absolutely required for this mirror symmetry," he said. "In the absence of IGF function, you lose information from the sensory axons of the nose to one half of the bulb."

Axons from the nose appear to express receptors for IGF on their growth cones, which allow the growth cones to essentially sniff out the IGF in the olfactory bulb and follow the trail to the proper target cells. Without the IGF produced in the olfactory bulb, the growing axons do not make the turn-off to the outer half of each bulb, but instead go only to the inner side nearest the midline of the brain.

Both of the IGF protein's forms, dubbed IGF-1 and IGF-2, are expressed by cells in the olfactory bulb, as determined by DNA microarray screens and other techniques.

While IGF appears critical in the early stages of olfactory development, when the basic architecture of the olfactory bulb is being set up in the fetus and perhaps also after birth, other axon guidance cues are no doubt needed to more finely direct the growth of axons, Ngai said. He is continuing to investigate these other cues, and also to map the nose's chemical receptors to specific areas of the bulb. Ngai and his colleagues also are following up on some early leads indicating that IGF may serve as a chemoattractant in other parts of the developing brain.

"We are seeing an emerging picture with IGF," Ngai said. "Over the past three years, there have been studies from others showing a role for IGF signaling in establishing the shape of certain neurons, and other studies showed that IGF is required for how fast axons grow. The present study tells us that IGF is actually being used as a chemoattractant. This is a new role for IGF in development."

Ngai's coauthors are former UC Berkeley graduate students Jonathan A. Scolnick and Cynthia D. Duggan, Kai Cui and Xiao-bing Yuan of the Institute of Neuroscience at the Chinese Academy of Sciences, and Shouhong Xuan and Argiris Efstratiadis of the Department of Genetics and Development at Columbia University Medical Center.

The research is supported by grants from the National Institute on Deafness and Other Communication Disorders and the National Cancer Institute of the National Institutes of Health, the Natural Science Foundation of China, and a gift from the Berrie Foundation.