This last week one of my neuroscience heroes, Rita Levi Montalcini, passed away at the age of 103. In her honor, I decided to repost a post I wrote a few months ago about one of her greatest contributions to science: nerve growth factor. In addition there’s a nice profile of her and her work in Nature. Here’s the repost:
A Neuroscience Field Guide: Nerve Growth Factor
Nerve growth factor, NGF for short, is a soluble protein that is secreted by various tissues in the body, and it promotes the growth of nerve cell processes and survival of neurons. It is the first of a class of molecules known as neurotrophins which are very important for the development and function of the nervous system.
What is remarkable about NGF is how it was discovered and by whom. NGF was discovered by Rita Levi-Montalcini an Italian, Jewish young doctor. She originally became interested in a set of experiments by renowned embryologist Viktor Hamburger which had observed that removing a limb bud from a chicken embryo caused the sensory neurons that innervated the undeveloped limb to die off. This suggested that there was something about the target tissue that promoted neurons’ survival in the embryo.
Levi-Montalcini had just graduated from medical school when Mussolini issued the “Manifesto per la Difesa della Razza”, which ultimately led to a ban of all non-Aryans from having professional and academic careers. Undaunted, Levi-Montalcini set up a laboratory in her bedroom in her parents house and then after the bombing of Turin in her family’s country cottage. After the War she was invited to St. Louis, MO to join Viktor Hamburger where she remained for many years and where she performed her Nobel Prize-winning research.
One of her initial observations was that if you implant specific mouse tumor cells on a chick embryo, sensory neurons will grow rapidly and sprout new axons which will innervate the tumor cells, again confirming that certain target tissues can promote nerve growth in embryonic tissues. The question was how did the target tissues do this? The key experiment came when she and her colleagues grew on one end of a cell culture dish some of these mouse tumor cells, and on the other a bit of neural tissue known as a sensory ganglion. After a few days, she observed that the neurons in the sensory ganglia grew a bunch new axons, and these axons seemed to be oriented toward the tumor cells. As if they were being attracted. This told her that the tumor cells were actually releasing some soluble factor into the growth media. The factor promoted growth of nerve cells and helped them live longer in a culture dish. This factor was later isolated by biochemist Stanley Cohen and shown to be a protein which they dubbed, imaginatively, nerve growth factor. Both Cohen and Levi-Montalcini received Nobel Prize in 1986.
How does NGF work? Now we know that NGF, as well as several other similar proteins known as neurotrophins, activate receptors in target cells which are called tyrosine receptor kinases, or Trk. Trks are proteins which are on the surface of neurons that when activated by NGF cause a series of cellular processes which cause embryonic neurons to grow new axons and to survive. Any cells which do not find their target will undergo a self-destructive process called apoptosis, thus help in the developing nervous system keep appropriate connections and eliminate inappropriate ones. Furthermore, NGF could form the basis of new therapies for treating various degenerative brain disorders and maybe promote neural regeneration after injury.
Rita Levi-Montalcini is now 103 years old, the oldest living Nobel laureate. Apparently she uses NGF eye-drops daily (it’s true!).