Creating and sculpting cells and organs that develop in the embryo requires the construction signals to be delivered at the right place and the right time. It was long presumed that the main cues come from molecular signals produced and sent out from distant and specialised glands, but as it turns out, this process also operates on a local scale. Many types of cell send out factors that influence the growth and development of other cells nearby, and the 1986 Nobel Prize in Physiology or Medicine rewarded the two scientists who first revealed this localised signalling system.
While investigating how the nervous system grows and develops, Rita Levi-Montalcini observed that transplanting mouse tumours into chick embryos induced an enormous outgrowth of nerves, regardless of whether the tumour was grafted inside or outside the sac containing the embryo. Levi-Montalcini’s proposition that the tumour was somehow releasing a growth-promoting substance for nerves flew against the popular view. With single-minded determination she successfully proved her idea, showing that a halo of fibres sprouted like sun rays from embryo nerve cells when they were grown close to tumour cells in cultures. Further investigations showed that this so-called nerve growth factor, or NGF for short, is released by many types of cell looking for new nerve connections. Nerve cells grow towards the source of NGF, allowing fibres to find their intended destinations and take on their assigned function.
The fortuitous discovery by Levi-Montalcini’s colleague Stanley Cohen that snake venom and mammalian salivary glands are rich sources of NGF provided Cohen with the materials to successfully purify the protein and determine its structure. He also noticed that salivary gland extracts were exerting non-nerve related growth effects in newborn mice, with their eyelids opening and teeth appearing prematurely. Correctly attributing this effect to another growth-inducing substance, which he termed epidermal growth factor, or EGF, Cohen and his co-workers went on to define the many ways in which EGF can influence major growth and development processes in an embryo. Though it took decades for their concepts to be fully accepted, Levi-Montalcini’s and Cohen’s discoveries revealed how cells talk and listen to each other, and paved the way for many other growth factors to be discovered.
By Joachim Pietzsch, for Nobelprize.org
This Speed read is an element of the multimedia production “Nerve Signaling”. “Nerve Signaling” is a part of the AstraZeneca Nobel Medicine Initiative.
Their work and discoveries range from how cells adapt to changes in levels of oxygen to our ability to fight global poverty.
See them all presented here.