The Journal of Neuroscience, October 1988, 8(10): 35353540 part of the Journal. Our intention is to present brief essays on Feature Article subjects of broad importance to neuroscientists, including his- Readers will notice a new addition to this issue. The following torical accounts, tributes to prominent figures, reports of impor- article by Viktor Hamburger is the first of a series of general tant advances, and other noteworthy issues in our field. interest articles that the Editors plan to include in the Journal The Editors welcome the response of subscribers to the intro- pages. Because of the backlog of primary research reports (see duction of this feature section. Further, we are happy to receive Society for Neuroscience Newsletter, Vol. 19, No. 2 (March/April), spectjic suggestions from subscribers for future articles. 1988, pp. 6-7), feature articles will appear only occasionally at first. As the backlog and the resulting publication delays are diminished, however, we plan to make such features a regular Dale Purves, Editor-in-Chief Ontogeny of Neuroembryology V. Hamburger E. V. Mallinckrodt Distinguished Service Professor Emeritus, Washington University, St. Louis, Missouri 63130 This essay commemorates the 100th anniversary of the birth protoplasmic connections are transformed into nerve fibers. The of neuroembryology. One cannot, of course, ascribe the begin- more refined versions of the reticular theory of the 1870s and ning of a branch of science to a single year, but the years between 1880s associated with the names of Golgi, Hensen, Gerlach, 1885 and 1890 saw major publications by the German anato- had one important point in common: nerve fibers were supposed mist Wilhelm His (183 l-l 904) and the Spanish histologist S. to be the product of a preneural protoplasmic network, referred Ramon y Cajal(l852-1934) both of whom laid the foundation to as plasmodesms, which, from the outset, connects the central to our present understanding of the structure and embryonic nervous system with its targets. According to some, the plas- origin of the nervous system. modesms originated by incomplete separation of postmitotic Modem developmental neurobiology emerged from the con- cells; according to others, the plasmodesms were formed sec- vergence of two traditions that had their roots in quite different ondarily as bridges between cells. The major problem of how and separate fields of inquiry, and with different conceptual and the plasmodesms were transformed into nerve fibers remained methodological frames of reference. The one, the histogenetic unresolved. tradition, was descriptive and became sophisticated through re- It is against this background that Wilhelm His’s conceptual fined technology. The other, experimental neuroembryology, was breakthrough to the neuron theory has to be judged. He was a causal-analytical and experimental, and was originally a modest native Swiss who had become Professor of Anatomy and Phys- side branch of general experimental embryology. iology at the university of his home town, Basel, at the young age of 26. (At that time the two disciplines were still combined The Histogenetic Tradition at most universities.) His’s title was somewhat deceptive; his The neurohistologists of the 1860s and 1870s among them 0. institute consisted of two rooms: one his office and laboratory, Deiters, had already worked out a clear picture of the neuron. the other a classroom for his 8 to 12 students that also housed It had been obtained by teasing out a motor neuron from the the anatomical collection. In time the department grew rapidly. adult spinal cord and clearly shows perikaryon, axon, and den- Later, His, who had a remarkably broad range of interests, be- drites (Fig. 1). Nevertheless, Deiters and his contemporaries came the Director ofthe Anatomy Department of the prestigious subscribed to the network or reticular theory of the structure of University of Leipzig and one of the leading figures of his gen- the nervous system. The impulse-conducting elements were pic- eration. Only a very independent mind of his stature could tured not as autonomous units but as part of a network of nerve accomplish a complete break with the tradition. fibers in which the cell bodies and dendrites were of subordinate In the early 1880s he began to concentrate on the development importance. Many thought of them as nutritive elements. An of the nervous system. When he looked at the spinal cords of earlier version of the reticular theory dated back to Theodor a series of early human embryos he recognized at once that they Schwann, one of the founders of the cell theory. He had pos- are not composed of a syncytium but of a layer of individual tulated that the cells bearing his name form cell chains whose epithelial cells. He described correctly the neural tube, the pre- cursor of the central nervous system, as a flat epithelium, which became columnar and then loosened up to form what he ap- This essay is based on a lecture delivered in November 1987 at the 13th Annual propriately called the spongy layer, the spongiosa. He identified Meeting of the Society for Neuroscience. Correspondence should be addressed to Professor V. Hamburger, Washington it as the precursor of the ependymal layer, that is, a glial struc- University, Department of Biology, St. Louis, MO 63 130. ture. The mitotic cells at the inner lining of the tube, which he Copyright 0 1988 Society for Neuroscience 0270-6474/88/103535-06$02.00/O called “germinal cells,” had been observed before him, but he 3536 Hamburger l Ontogeny of Neuroembryology Figure 1. Drawing of a neuron by 0. Deiters(1865). was the first to recognize that they were the precursorsof nerve plasmodesms,but were neither nourished nor transformed by cells. He observed that after their terminal mitosis they became them. Theseobservations formed the foundation of the concept pear-shapedand formed a protoplasmic outgrowth at their distal of the autonomous neuron on which the neuron theory is based. ends which he identified as the incipient axon. These young At the end of his classicalmonograph of 1886 he generalized neuroblasts, as he called them, supposedlymigrated acrossthe his findings: “I consider as a definitive principle the theorem spongiosaand assembledat the outer margin of the neural tube that every nerve fiber originates as the outgrowth of a single where they formed what he called the mantle layer. In this cell. The latter is its genetic, nutritive and functional center. All particular case, the neuroblastswere motor neurons. The tips other connections are either indirect or they originated second- of their axons pierced through the external limiting membrane, arily” (1886, p. 5 13). By genetic he meant embryonic. Among formed a bundle, the motor nerve, and grew toward their target, His’s other discoveries<the neural crest and the derivation of the somites. They were perhaps supported and guided by the spinal and sympathetic ganglia from this structure, and the ob- The Journal of Neuroscience, October 1988, 8(10) 3537 servation that dendrites (which were named by him) always say not, if we consider only his early work on the cerebellum. differentiate later than axons. But the embryonic nervous system captivated his interest in its Implicit in His’s theorem is the idea that there is contiguity own right, and he began to study the embryonic spinal cord. At but not continuity between nerve cells and other nerve cells or that time, in his seclusion in Barcelona, he was cut off from the their targets. However, his histological methods did not permit mainstream of anatomical research and was not aware of His’s him to demonstrate cell-to-cell contact as a fact. It is at this investigations. As a result he rediscovered in chick and mam- point that Ramon y Cajal enters the stage. He was a genius in malian embryos the early history of the neuroblast and the science and an extraordinary human being. One can glean from outgrowth of the axon. In 1890, His sent him his publication his delightful autobiography (1937) the magnetism of his per- and Cajal acknowledged later the priority of His. sonality-a personality that was certainly more colorful than In 1890 Cajal made what he described as one of his most that of Herr Geheimrat His. But his most outstanding trait was cherished discoveries: the growth cone. “In my sections of the his iron will, which he had inherited from his father, and his 3-day chick embryo, this ending appeared as a concentration of singleness of purpose. Cajal, who was 20 years younger than protoplasm of conical form, endowed with ameboid move- His, was born in a small, desolate mountain village in northern ments. It could be compared to a living battering ram, soft and Spain where he received very little formal education. Although flexible, which advances, pushing aside mechanically the ob- this lack of education was largely his own fault, he managed to stacles which it finds in its way, until it reaches the area of its enter professional life. Up to 1887 he had done rather undis- peripheral distribution. This curious terminal club I christened tinguished work in histology at the University of Valencia, but the growth cone” (1937, p. 369). To this day, the growth cone in 1887 he moved to Barcelona and, according to his own tes- has remained one of the major challenges to neuroembryolo- timony, this year was of decisive importance. On the occasion gists. Of the many other embryological discoveries of Cajal I of a visit to Madrid, a colleague showed him microscope slides mention only one: the mass migration of embryonic neurons. of nerve tissue treated with Golgi’s silver impregnation method. He observed the details of the differentiation of the granule cells The method had been available since 1873, and Golgi had made in the cerebellum.