Spotting desmosomes: the first 100 years.

The desmosome is an elegant, highly organized structure vital to our survival. The term was coined by Josef Schaffer in 1920 (Schaffer, 1920) and derives from the Greek word desmos, meaning “bond“, ”ligament“ or “fastening“, with “some” meaning “body“ (Wood, 1959; Mazzarello et al., 2001; Wells, 2005). The identification of this structure, however, dates back to the 19th century during an explosion of biomedical discoveries. At this time, continental Europe was at the forefront of medical research, Germany was the powerhouse of general pathology, and medical practitioners began to recognize a correlation between clinical symptoms and physical examination findings (Margreth, 2001). Improvements to the compound microscope during this period introduced a powerful tool that opened the world of cellular pathology, and formed the foundation for developing new theories of disease based on the analysis of affected cells (Mazzarello et al., 2001; Appendices A and B). As advances continued to be made in light microscopy, the biological literature was filled with reports describing contact points between cells in tissues and defining them as “intercellular bridges”. It was not until 1864 that a young Italian pathologist, Giulio Bizzozero (1846–1901), gave the first description of desmosomes. In his examination of the stratum spinosum, he noted small dense nodules at the contact points between adjacent cells, which were subsequently termed “nodes of Bizzozero”. He correctly interpreted these nodes as points of cell–cell adhesion where adjacent but separate cells contributed (Bizzozero, 1864, 1870). Bizzozero’s observations are impressive considering the tools that were available and that his interpretation ran counter to prevailing opinion, dominated by Louis Ranvier’s theories on cell–cell continuity, in which these nodes were interpreted as intercellular bridges consisting of continuous cytoplasm through which filaments passed from one cell to another (Ranvier, 1882; Wood, 1959; Fawcett, 1961; Mazzarello et al., 2001; Wells, 2005). By the time Schaffer coined the term desmosome, medical biology was entering a period of decline spanning World War I (1914–1918) and World War II (1937–1945) (Rasmussen, 1997; Margreth, 2001). After this period, analytical biology was revived and quickly became a fast-evolving frontier heralded by the first electron micrograph of a cell by Keith Porter, Albert Claude and Ernest Fullman at the Rockefeller University (New York) in 1944 (Porter et al., 1945). This revolutionary technique provided detailed analysis of subcellular distances, dimensions and fine structures, allowing Porter (1912–1997) to confirm Bizzozero’s original interpretations 90 years later. Subsequent refinement of electron microscopic techniques revealed the lack of continuity between adjacent cells, regular electron-dense plates separated by a uniform light space, with tufts of fibrous material extending from the membrane to the cell interior (Porter, 1956). In 1958, George Odland (1922–1997) gave the first description of these electron dense plates using densitometric analysis, which allowed him to reinterpret the ‘nodes of Bizzozero’ as a pair of attachment plaques, one from each adjacent cell. These nodes specifically had seven intervening layers of different density that occupied a 350 A space with fibrils terminating at the attachment plaques. These plaques were electron-dense ovals measuring 0.3–0.7 μm in diameter and greater than 100 A in thickness. Together, these observations indicated a much higher degree of desmosomal organization than previously presumed (Odland, 1958).