One hundred years of interstitial cells of Cajal

This review is a portrayal of the evolution of ideas involving the interstitial cells of Cajal in changing disguises as dull fibroblasts, not very exciting Schwann cells, or perhaps quite important, though primitive neurons. However, today unmasked (we believe), they reveal themselves as myoid cells, a role that, judging by current interest, is far more exciting than former ones. Close to 500 publications from 1860-1999 have contributed to the discussion in one way or the other. This literature contains a wealth of correct observations but obviously also wrong interpretations, which are seen as a result of too blind a belief in specificities of visualization methods, combined with a desire to interpret even the hidden detail. It has been my objective to attempt to trace the origins of viable ideas, and I have therefore focused on relatively few authors. The most recent development from 1980 until today is so well covered by easily accessible reviews that I have resorted to a mere, but hopefully complete, list of them. Modern ICC'ists have so far been caught in the external muscle of the gut and kept their hands off its internal affairs. However, while working my way through the literature it struck me that a number of recent studies may provide the elements of a plausible model for the villous contraction mechanism. In the present context, an important point is that the very first published interstitial "neurons" from Cajal's hand-of the intestinal villus, 1889-may achieve new significance as a possible correlate to the regulatory ICC of the intestinal muscularis. Partly to make this point, I have taken the liberty of giving a short account of recent results from our lab.