Elsevier

Brain Research Bulletin

Volume 49, Issue 5, 15 July 1999, Pages 305-315
Brain Research Bulletin

History of Neuroscience
The history of radial glia

https://doi.org/10.1016/S0361-9230(99)00065-9Get rights and content

Abstract

Radial glial cells are now recognized as a transient population that serves as scaffolding for neuronal migration. The recognition of the existence and role of radial glia has not been smooth, and here we provide a brief historical overview on the pioneering studies on this subject. The histologists and embryologists Albert Kölliker and Wilhelm His performed seminal investigations on cortical morphogenesis in the last decades of the 19th century. However, the introduction of the silver impregnation Golgi technique, and its diffusion in the late 1880s, played a crucial role in the detection of radial glial processes. The radial arrangement of fibers emerging from the neuroepithelium lining the central canal was initially detected in the embryonic spinal cord by Camillo Golgi himself. The first Golgi impregnation of the cerebral cortex of mammalian fetuses was performed by Giuseppe Magini, who detected radial fibers extending from the ventricular neuroepithelium, and observed cells intercalated along these processes. Radial fibers, regarded as epithelial or ependymal processes, were then observed in the developing spinal cord and cerebral cortex by several investigators. Santiago Ramón y Cajal was the first to suggest that radial fibers were modified astrocytic processes functioning as a support during cortical histogenesis. Cajal acknowledged Magini’s findings, but he criticized Magini’s observations on the existence of neurons along radial fibers. With the advent of electron microscopy, the existence of radially arranged glial processes along which young neurons migrate was finally ascertained in the early 1970s by Pasko Rakic, thus opening a new era in the cellular and molecular biology of radial glia.

Introduction

Radial glia is a specialized cell type belonging to the astroglial cell lineage. During development, these long bipolar cells expand radially across the thickness of the cerebral wall. Neuroblasts migrate along the elongated radial glial fibers, which disappear after neuronal migration has been completed, when the morphology of radial glial cells changes into that of astrocytes (see [42] for review).

The role played by radial glia in neuronal migration was ascertained by Rakic in the early 1970s 38, 39, 40, but radial glia was discovered in the last decades of the 19th century and these pioneering studies stimulated debates on the morphogenesis of the nervous system and, in particular, of the cerebral cortex [3].

At the end of the 20th century, in an era in which studies on neuronal migration are on the forefront of neurosciences, we wish to recall the scientific itinerary that brought the discovery of radial glia and its role in the migration of neuroblasts. In particular, we will focus on archival material that is not readily accessible to modern neuroscientists.

Section snippets

The early leading authorities in the study of cortical development

Rudolf Albert von Kölliker (1817–1905) and Wilhelm His (1831–1904), two illustrious Swiss scientists, exerted a profound influence on the studies of the development of the nervous system, including the cerebral cortex. They also played an important role in the birth and diffusion of the “neuron doctrine” 18, 54. Kölliker is considered to be the father of modern histology, as he influenced two generations of morphologists in the second half of the 19th century. Kölliker’s famous manual of

The black reaction and the first Golgi impregnation of developing nervous tissue

Radial glial cells were first fully visualized by Golgi staining and this technique played a crucial role in the history of radial glia. As is well-known, Camillo Golgi (1843–1926) reported in 1873 that he had found a new stain of the nervous tissue, based on the hardening of tissue with potassium dichromate followed by impregnation with silver nitrate [10] (see also 33, 36). The report of the technique, which was presented in just a few lines in the introductory paragraph of an article without

Magini and the first Golgi impregnation of the developing cerebral cortex

In the mid-1880s, Giuseppe Magini (1851–1916) became interested in the morphogenetic events of the cerebral cortex, probably stimulated by Kölliker’s studies, which he quoted extensively [25]. Magini was at that time an assistant professor of Histology and General Physiology at the University of Rome, and he became full professor in the same university in 1894 [8]. Magini applied the Golgi method to the study of cortical development as soon as this novel technology became available. In his

“Like the grains of a rosary”: the beaded radial neuroglia

The paper delivered by Magini in Pavia in September 1887 [25] was based on the fetal cerebral cortex of several mammals (rabbit, dog, guinea pig, calf), including man, and primarily on human fetuses in the 7th–9th month of gestation and calf fetuses in the 6th and 7th months of gestation. Magini used carmine and hematoxylin stains, but obtained “precise findings” only with the Golgi impregnation technique. Thus, he reported in Golgi-stained material (here we provide a translation of parts of

Cajal and Magini

Santiago Ramón y Cajal entered early the scene of research on radial glia. An undisciplined, creative, and passionate anatomist, he was searching for novelties and inspiration, and had the chance to observe for the first time Golgi-impregnated sections in Madrid when he visited the psychiatrist José Simarro y Lacabra in 1887. Cajal’s mind immediately burned of excitement [49]. In a burst of feverish activity, he became fully devoted to the study of the nervous system by means of the Golgi

Toward glial scaffolding

With the diffusion of the Golgi technique in Europe, many investigators began to work on the developing nervous tissue (which is impregnated by Golgi staining more effectively than the adult nervous tissue). As in the initial studies by Golgi [11] and Cajal [43], stained filaments radiating out from the epithelium lining the central canal toward the pial surface were detected in the embryonic spinal cord 22, 51. Michael von Lenhossék (1863–1937) noticed migrating glial cells, which were

The “varicosities” reach the status of migrating neuroblasts

The modern history of radial glia (see [42] for review) is beyond the scope of our historical outline. It is, however, important to recall that the solution of the problem of radial glia has required a remarkable effort even after electron microscopy and tritiated thymidine autoradiography were already widely in use.

Investigating the development of the rat cerebral cortex (with autoradiography, as well as the Nissl and Golgi stains), Berry and Rogers [5] described that long processes of

Acknowledgements

The authors thank Prof. M. Lambiase for providing original reprints of Magini’s studies, Prof. E. Pannese for his advice, Prof. A. Barasa for providing the original photographs used for the illustrations of Godina’s article, Prof. K. Kristensson for his help in the bibliographic search, Prof. A. Calligaro for allowing the consultation of the documents kept at the Museum of the History of the University of Pavia, and Prof. V. Vannini for allowing the consultation of material kept in the

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