Pio del Rio-Hortega introduced the concept of microglia (Fig. 1) as a defined cellular element of the central nervous system in a book chapter called “Microglia” (208) written for the landmark publication Cytology and Cellular Pathology of the Nervous System, edited by Wilder Penfield in 1932. In this visionary article, which we strongly recommend to read in original, del Rio-Hortega postulated the following:
1) microglia enter the brain during early development.
2) These invading cells have amoeboid morphology and are of mesodermal origin.
3) They use vessels and white matter tracts as guiding structures for migration and enter all brain regions.
4) They transform into a branched, ramified morphological phenotype in the more mature brain (known today as the resting microglia).
5) In the mature brain, they are found almost evenly dispersed throughout the central nervous system and display little variation.
6) Each cell seems to occupy a defined territory.
7) After a pathological event, these cells undergo a transformation.
8) Transformed cells acquire amoeboid morphology similar to the one observed early in development.
9) These cells have the capacity to migrate, proliferate and phagocytose.
All these statements are perfectly valid today and could appear in a modern textbook of neuroscience without the smallest change.
The origin of microglia has been debated for a long time. There were arguments that these cells stem from the
neuroectoderm (271). Today there is general consensus that microglial cells are derived from progenitors that
have migrated from the periphery and are from mesodermal/mesenchymal origin (for review, see Ref. 138).