The Significance of Neuronal Cell Death During the Development of the Nervous System

Abstract

It would seem to be a paradox that death of neurons should play a significant role during ontogenesis. Therefore it is understandable that it took a long time for this phenomenon to be generally accepted. Cell death was reported at the beginning of this century by Collin (1906) and by Mühlmann (for references see Ernst 1926). In 1926 Ernst, stimulated by Kallius, published an extensive study on cell death in vertebrates during normal development, after he had carefully investigated no less than 1000 serially sectioned specimens from 32 species. He found that cell death was such a common and widespread phenomenon that it needed systematic investigation to be understood. Although Ernst speculated about endogenous and exogenous factors which might cause embryonic cell death, these factors were not generally accepted. Kallius (1931) emphasized another viewpoint. Instead of looking for mechanisms leading to cell death, he analyzed cell death as a mechanism involved in morpho-, histio- and phylogenesis. Twenty years later, Glücksmann (1951), a former student of Kallius, continued with his teacher’s ideas and classified cell degenerations according to their developmental functions. He distinguished morphogenetic, histiogenetic and phylogenetic degenerations. Morphogenetic degenerations were thought to precede or accompany changes in the form of organs; histiogenetic degenerations occur during differentiation of tissues; phylogenetic degenerations are related to vestigial organs and to the regression of larval structures. These distinctions are, however, merely descriptive and do not reveal any developmental mechanisms leading to cell death. Our interest is now to further the ideas of Ernst and search for mechanisms leading to neuronal cell death.