Cajal’s contribution to the knowledge of the neuronal cell nucleus

Abstract

In 1906, the Spanish neurobiologist Santiago Ramón y Cajal was awarded the Nobel Prize in Physiology or Medicine in recognition of his work on the structure of neurons and their connections. Cajal is commonly regarded as the father of modern neuroscience. What is less well known is that Cajal also had a great interest in intracellular neuronal structures and developed the reduced silver nitrate method for the study of neurofibrils (neurofilaments) and nuclear subcompartments. It was in 1903 that Cajal discovered the "accessory body" ("Cajal body") and seven years later, published an article on the organization of the cell nucleus in mammalian neurons that represents a masterpiece of nuclear structure at the light microscopy level. In addition to the accessory body, it includes the analysis of several nuclear components currently recognized as fibrillar centers of the nucleolus, nuclear speckles of splicing factors, transcription foci, nuclear matrix, and the double nuclear membrane. The aim of this article is to revisit Cajal's contributions to the knowledge of the neuronal nucleus in light of our current understanding of nuclear structure and function.

Purkinje Cell Degeneration in pcd Mice Reveals Large Scale Chromatin Reorganization and Gene Silencing Linked to Defective DNA Repair

“…In control PCs, H4K20me3-positive heterochromatin was restricted to a few masses associated with the nucleolus and nuclear envelope (Fig. 3, A and C), mainly corresponding to the previously described constitutive centromeric heterochromatin (4,5,36). In the pcd mice, numerous PCs exhibited large domains of the genome enriched in the repressive mark H4K20me3.…”

Cajal bodies in neurons

“…1F). 3,15 Moreover, the nuclear pattern of "neutrophil granules" is similar to the nuclear foci observed in neurons after a short pulse of 5 0 -fluorouiridine incorporation into nascent RNA, which also are excluded from "hyaline grumes/nuclear speckles" (Fig. 1G, H).…”

“…Therefore, Cajal is recognized as the father of modern neuroscience. 2,3 While the Golgi stain was a fundamental tool in characterizing neuronal populations and their connections in nervous centers, little progress had been achieved in the characterization of neuronal intracellular structures by the end of the 19 th century. Dissatisfied with the available staining techniques, in 1903 Cajal developed a simple and reliable procedure for demonstrating diverse cellular structures, the "reduced silver staining method."…”

“…[5][6][7][8] Having at hand the reduced silver staining method, in 1910 Cajal published an extensive monograph on the nuclear organization of the pyramidal neurons of the cerebral cortex, which represents a masterpiece of nuclear structure at light microscopy level. 3,9 In the early 1900s, knowledge of the neuronal nucleus was essentially based mainly on the use of acid and basic aniline dyes which revealed the basophilic framework of "Flemming's chromatin." 9 Other nuclear structures revealed with aniline dyes at that time were the "nucleolus" -the site of rRNA synthesis, rRNA processing and preribosomal particle assembly 10,11 -and the "Levi basophilic grume," a nucleolusattached clump of centromeric heterochromatin.…”

“…1). 3,9 Fig. 1A shows Cajal's original drawing of these nuclear structures and recent parallel images of the neuronal nucleus processed with modern specific molecular markers of nuclear compartments.…”