Nerve growth factor activation of differentiation programs in neuronal and non-neuronal cell lines from amphibians to mammals

Nerve growth factor activation of differentiation programs in neuronal and non-neuronal cell lines from amphibians to mammals

413 1 Nerve Growth Factor activation of differentiation programs in neuronal and non-neuronal cell lines from,amphibiarrsto -1s. Rita Levi-Montalci...

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Nerve Growth Factor activation of differentiation programs in neuronal and non-neuronal cell lines from,amphibiarrsto -1s.

Rita Levi-Montalcini

The Nerve Growth Factor (NGF) was first discovered and is known for its most potent growth promoting activity on immature sensory and immature and fully differentiated sympathetic nerve cells. NGF does not only markedly enhance neurite outgrowth and/or regeneration of axons from these cells, but it plays a key role in their survival and differentiation and exerts a neurotropic action on their nerve fibers. Evidence has been obtained that this protein molecule, first purified from mouse salivary glands and then found also Iin large amounts in male organs of other vertebrates, is synthesized in minute amounts by most vertebrate neoplastic and aormal cell lines. Very recent work has resulted in the isolation of mouse and human NGF genes and in the localization of the human NGF on the proximal short arm of chromosome 1.

Although the NGF mechanism of action is still largely unknown, it has been unambiguously proven that NGF binds to specific receptors located on the target cell perikarya and on their axon endings. The NGF-receptor complexes are retrogradely transported from the nerve fiber endings to the cytoplasmic compartment where this growth factor is found in several intracellular organelles.

Studies during this last decade have shown that NGF does not only exert its action on sensory and sympathetic nerve cells, but also channels chromaffin stem cells and neoplastic chromaffin cells toward the neuronal rather than the glandular cell phenotype. Work now in progress in our laboratory has also provided evidence that mouse NGF promotes growth and differentiation of several intracerebral neuronal cell lines in lower vertebrates (amphibians) and enhances differentiation and function of mast cells in neonatal and adult rodents. It will be the object of this presentation to describe and comment on the results of these most recent studies performed in the amphibian Xenopus Laevis tadpoles and in rodent foetuses.