THE DEVELOPMENT OF THE PERIPHERAL NERVE FIBRE
Version of Record online: 21 JAN 2008
Volume 35, Issue 3, pages 283–323, August 1960
How to Cite
HUGHES, A. (1960), THE DEVELOPMENT OF THE PERIPHERAL NERVE FIBRE. Biological Reviews, 35: 283–323. doi: 10.1111/j.1469-185X.1960.tb01326.x
- Issue online: 21 JAN 2008
- Version of Record online: 21 JAN 2008
- Received 3 September 1959
- 1Theodore Schwann, in hisstudy on the cellular nature of animal tissues (1839), was the first to describe the development of peripheral nerves. He believed, however, that the nerve fibre was formed by fusion of a row of the cells, which have since borne his name, but which are now known to form only the sheath around the nerve fibre. The latter has a wholly separate origin.
- 2The developing peripheral nerves of the tail of amphibian larvae have been studied by a series of authors, the first of which was Schwann himself. Hensen (1864) realized that in their earliest stage the nerves of the tail fin were devoid of nuclei. In the 1870?s, several authors described the apparent origin of nuclei there in de now. In 1886, however, Kölliker followed the multiplication by mitotic division of Schwann cells, to which, as he realized, belong all the nuclei associated with the developing nerve fibre.
- 3Balfour (1876) maintained that the whole of the peripheral nervous system in elasmobranchs was formed from cells which migrated outwards from the spinal cord. Hensen (1876) believed that nerves were formed along the tracks of protoplasmic strands which ran the whole distance between centre and periphery, and which originated in the incomplete cleavage of cells in the ectodermal layer of the early embryo. These theories were opposed to the views of Bidder & Kupffer (1857), His (1879), and Ramon y Cajal(1890) all of whom described the development of peripheral nerves in terms of the outgrowth of fibres from cells within the spinal cord and ganglia.
- 4Ramon y Cajal was the first to study the developing nervous system by metallic impregnation methods. He concluded that no fusion occurs at points where the processes of neighbouring cells come into contact. The concept of cellular individuality in the nervous system was the basis of the Neurone Theory of Waldeyer (1891).
- 5The first attack on this theory came with the work of Apathy (1889) who claimed to be able to follow stainable fibrillar constituents of the nerve fibre, the ‘neurofibrilla’, through the junction of one nerve cell with the next. Apathy stated that they were the actual conducting elements of the nervous system. The study of neurofibrillae in the developing nervous system by various workers has led to no uniform concepts. Paton (1907) believed that they can enter the nerve cell from outside; Held (1909) claimed that a pre-existing network served as a guide from the growing nerve fibre. In this respect Held's views approximate to those of Hensen.
- 6Fresh support to the neurone theory was gained in the pioneer experiments of Ross Harrison (1907) in the cultivation of tissues in vitro, in which he observed the outgrowth of living nerve fibres from amphibian neuroblasts into a medium of clotted fibrin. In the course of their growth such fibres received no support or any contribution from adjacent cells. Harrison described the detailed behaviour of the terminal growth cone, which had already been discovered by Ramon y Cajal.
- 7Research on the outgrowth of nerve fibres has so far been largely confined to vertebrate embryos, though the ingrowth of axons from epidermal sensory cells in insects has been studied in recent years (Wigglesworth, 1953). In some invertebrates axons undergo an apparent secondary fusion to form giant fibres (Young, 1936), though the development of this condition has not yet been followed.
- 8The outgrowth theory by itself leaves unexplained the forces which direct the nerve fibres during their growth. His (1887) believed that the fibre grows straight outwards until deflected by some structure lying across its path. Ramon y Cajal (1893) suggested that the outgrowing tips of nerve fibres were attracted towards their end organs by a chemotropic stimulus. Weiss, on the basis of experimental study on tissue cultures (1934), has elaborated a theory whereby a growing organ orientates intercellular material around itself, and so provides a pre-formed pathway along which a growing fibre, with its accompanying Schwann cells, can reach its destination. Contact with surfaces is certainly an important factor in nerve outgrowth.
- 9The mutual interactions of Schwann cells and nerve fibres in the living state have been extensively studied by Speidel(1932 onwards) in the tail fin of amphibian larvae. The progress of myelination is now being followed by means of the electron microscope (Geren, 1954).
- 10Whatever the forces which direct growing nerve fibres, it is clear that there is no complete and detailed plan set before the unfolding peripheral nervous system from the outset, for some individual fibres choose random and aberrant paths. Ramon y Cajal (1908) was the first to point out the significance of these ‘fibres égarées’.
- 11Although no direct experimental proof of chemotropic attraction of nerve fibres has been obtained, chemical forces are invoked in the adjustments which follow when a nerve has approached its end organ. On the motor side Weiss (1936) found that in Amblystoma grafted supernumerary limbs move in unison with an adjacent normal member. Corresponding muscles contract synchronously even though the anatomical pattern of their regenerated nerves may be aberrant. Weiss explained this ‘resonance effect’ by postulating that when a regenerating motor nerve reaches a muscle at random, a chemical stimulus is transmitted centripetally, which leads to rearrangement of central synaptic junctions. Similar readjustments are inferred in the experiments of Sperry (1951) in which areas of skin on the body surface of a tadpole are interchanged. A grafted patch continues to transmit to the centre information concerning location of the body surface which refers to its original site even though in its new position it is innervated by surrounding cutaneous nerves.