How do growing nerve cells find their targets?

Credit: Nobel Foundation
In 1949, Rita Levi-Montalcini noticed something unexpected. Her colleague Elmer Bueker had implanted tumors into chick embryos and found that nerves would invade the tumors, but what attracted nerves to tumors? Levi-Montalcini had noticed that the nerves were not just invading tumors: They were also invading the tissues near the tumors, even invading blood vessels downstream of tumors — suggesting that the tumors might have been releasing a diffusible nerve growth factor (NGF), a postulated substance that could guide either nerve differentiation, growth or survival. Levi-Montalcini proved the existence of NGF 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, Stanley Cohen, and colleagues purified NGF. NGF told us that the way nerves find even their normal targets is unexpectedly adaptive: nerves grow just about everywhere, and they die off where 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, which she did in a makeshift home lab that she set up hiding out from Nazis and fascists during WWII, from her autobiography, In Praise of Imperfection. Open the excerpt in Acrobat and you'll see some helpful notes in red.

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