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

Neuroscientists find IGF directs axon growth to set up brain's wiring

Berkeley — A human hormone known to stimulate the growth of cells throughout the body has a new role - helping to set up the proper nerve connections in the odor center of the brain, according to University of California, Berkeley, scientists.

The hormone, insulin-like growth factor (IGF), is well-known to biomedical researchers and has been tested as a therapy for diabetes and some growth disorders. Until now, decades of research have turned up only one solid role for IGF, however, and that is to makes cells grow and multiply.

Neuroscientist John Ngai, Coates Family Professor of Neuroscience and director of the Functional Genomics Laboratory at UC Berkeley, and his colleagues have now found that IGF plays a critical role in setting up the connections between chemical detectors in the nose and the brain's olfactory centers. These centers, the olfactory bulbs, are a pair of raisin-sized structures in the front part of the brain that analyze signals from the many odor receptors in the nose.

IGF joins a small number of identified molecules known to direct the growth of nerve cells in the brain during its development, making it "another tool in the brain's tool kit for how you wire up the brain," Ngai said.

Aside from what this reveals about how the brain wires itself as it grows, these molecules could become important therapeutically once doctors begin implanting new cells, perhaps stem cells, into the brain to cure neurodegenerative diseases, Ngai said.

"Even if you figure out a way to grow new cells to replace dying cells, those cells still need to make proper connections," Ngai said. "So, anything you know about what drives normal connectivity in the brain will help you figure out how to get those new cells to wire up correctly."

Ngai and colleagues at UC Berkeley, the Shanghai Institutes of Biological Sciences in China and Columbia University Medical Center reported their findings in the March 27 issue of the journal Neuron.

The molecules netrin, ephrin, semaphorin, slit and now IGF are called axon guidance molecules because as nerves stretch their tentacle-like axons out into the brain to connect with other neurons, these molecules act as signposts to steer the axons to the correct brain cells. As the brain grows during early development to some 3 billion nerve cells, each nerve cell makes, on average, 10,000 connections with other nerve cells, so "guidance cues" are critical.

"Cells from the retina of the eye, for example, carry signals into your brain conveying information about the outside world, and these go back into your brain in a very ordered projection such that there is a topographic map of the visual world from the retina at each successive layer of relays in the brain," Ngai said. "Something must order those connections, or otherwise you wouldn't be seeing a coherent image."

So far, these axon guidance cues include chemoattractants that make axons grow toward them, and chemorepellants, which make them turn away. As shown by Ngai's colleagues in China, IGF is an attractant; the growth cones of axons turn toward higher concentrations of the hormone.