THE EXPERIMENTAL EMBRYOLOGY OF THE FOETAL NERVOUS SYSTEM

SUMMARY 1 It is feasible to submit the mammalian foetus to surgery and the types of operation thus far performed are reviewed. Other techniques for affecting mammalian organs during development, such as irradiation, organ explantation, and antibody-antigen reactions, are mentioned. 2 The reactions to injury of mammalian foetal nerve tissue are reviewed. The severed spinal cord does not regenerate under ordinary circumstances in postnatal or foetal animals. Spinal ganglion cells regenerate. The reactions of the nervous system to injury are more extensive in younger foetuses than in older ones, and more marked in foetuses than in postnatal animals. This is seen in the results of eye extirpation in guinea-pig foetuses compared with those in newborn rats. Gliosis is limited in foetal and young animals, and is not so marked in young foetuses as in old ones, owing probably to the immaturity of the neuroglial cells and to a relatively reduced glial cell number. 3 The life history of nerve cells can be divided into three stages: the phase of proliferation, the phase of differentiation, and the phase of maturation, including growth and the completion and maintenance of this process. The methods of determining which stage of development of neurones is affected after operation on a mammalian foetus are explained. 4 There are many cases in chick and amphibian embryos where cellular hypoplasia after operation is caused by retrograde or transneuronal regression or degeneration of cells, and is a result of effects on the maintenance of neurones, rather than on their proliferation or differentiation. 5 Cases of foetal malformations, such as lack of development of a limb or eye, are reviewed. The hypoplastic effects in these cases are reinterpreted and are seen to be due also to effects on the maintenance of neurones, not on their proliferation or differentiation. 6 Experiments on limb or eye removal in foetuses are reviewed. The resulting hypoplasia or surmised hypoplasia in the spinal ganglia, spinal cord, superior col-liculus and lateral geniculate body are caused partly by retrograde or transneuronal degeneration or regression and are interpreted as effects, at least in part, on the maintenance of neurones. More work must be done on mammals before effects on proliferation and differentiation of neurones can be eliminated as contributing to hypoplasia after operation. 7 The mammalian foetal experiments which produce hypoplasia after some or all of the nerve fibres have already reached their destination (limb, spinal cord, superior colliculus, lateral geniculate body) are not unlike many experiments producing hypoplastic effects in amphibian and chick embryos, where the nerve fibres have not yet innervated their respective parts at the time of operation. In both, the resulting hypoplasia is due, at least in part, to retrograde or transneuronal degeneration or regression of already differentiated nerve cells; it is frequently a direct effect on the maintenance of cells, rather than an indirect effect on proliferation or differentiation, and is produced by a rapid degeneration and disappearance of cells in which pathological changes are sometimes not observed. 8 The effects of similar operations on foetuses, newborn and very young mammals are compared. The reactions to eye removal occur much more rapidly in foetuses than in newborn or very young animals. The foetus is more favourable for experiments in embryology than postnatal animals. 9 Adult nerve fibres and cells possess an amazing degree of plasticity. Some examples are given. 10 The afferent nerve fibre supply is significant for the maintenance of nerve cells, not only during early maturation, but throughout the remainder of their life history. Cases of transneuronal degeneration of cells in the central nervous system are cited. A quantitative relation exists between the amount of reduction of the afferent nerve supply and the resulting amount of neuronal degeneration. Examples of this are given in chick embryos, mammalian foetuses after eye removal, and adult mammals. The actual size reached by neurones may be influenced and determined by the presence and number of afferent nerve fibres. Examples are given in amphibia and mammals. The reasons for the influence of afferent fibres on the maintenance of nerve cells are discussed. Afferent fibres may maintain nerve cells either by bringing impulses to the cell, or the presence of afferent fibres may be sufficient to maintain the cells. So-called functional degeneration of nerve cells and fibres is discussed, and it is concluded that this does not occur. Thus the chemical, not the physiological, attributes of afferent fibres are responsible for the maintenance of nerve cells.