History of the discovery of neuronal death in embryos.

The German anatomists, M. Ernst and A. Glücksmann, deserve credit for the discovery of widespread cell death in embryonic tissues, including the nervous tissue. In 1934, V. Hamburger described a significant hypoplasia in dorsal root ganglia (DGR) and lateral motor columns, following the extirpation of limb buds in chick embryos. In the early 1940s, Dr. Rita Levi-Montalcini in Turin (Italy) repeated the experiment and suggested that the hypoplasia might result from the death of young differentiated neurons. In a joint reinvestigation, published in 1949, large numbers of degenerating neurons were described in brachial DRG, following wing bud extirpations. In the same embryos, Dr. Levi-Montalcini observed massive neuronal death in cervical and thoracic DRG which had not been affected by the operation. This was the discovery of naturally occurring neuronal death. Long after the discovery of Nerve Growth Factor (NGF) it was recognized that NGF and natural neuronal death are two sides of the same coin: the latter results from an insufficient supply of the former by the target tissues.