How do growing nerve cells find their targets?

Rita Live-Montalcini (image credit)
In 1949, Rita Levi-Montalcini noticed something unexpected. Her colleague Elmer Bueker had found that nerves would invade tumors that he had implanted into chick embryos. What attracted the nerves to tumors? Indeed, how did nerves ever find their normal targets? What Levi-Montalcini noticed: the nerves would invade not just the tumors, but also the tissues near the tumors–suggesting that the tumors might have been releasing a diffusible nerve growth factor, a postulated substance that could guide either nerve differentiation, growth or survival. Levi-Montalcini proved the existence of a nerve growth factor by culturing just tumors and ganglia in the same dish, finding that the nerves from the ganglia would connect to tumors even in vitro. Later, she purified the key protein, now called Nerve Growth Factor (NGF). NGF told us that the way nerves find their targets is unexpectedly adaptive–nerves grow just about everywhere, and they die off if they fail to find targets. 
A short review: Aloe, L. (2004) Rita Levi-Montalcini: the discovery of nerve growth factor and modern neurobiology. Trends Cell Biol 14:395-9. 

Some amazing historical background: An excerpt about her pre-NGF work done in makeshift home labs she set up hiding out in the hills during WWII, from her autobiography, In Praise of Imperfection. Open the excerpt in the right pdf viewer and you'll see some helpful notes in red.

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