Blueprint of an ancestral neurosensory organ revealed in glial networks in human dental pulp.

Sensory function of human dental pulp has long been known. A composite role has been suggested for odontoblasts as sensory cells in addition to the synthesis of dentinal matrix. However, the neural basis for such a composite sensory activity remains enigmatic. Here, we aimed to probe the question by pursuing an evolutionary logic; if dental pulp is a vestigial sensory organ co-opted to a function of synthesis of mineralized matrix, essential elements of neurosensory organs may persist in dental pulp. Through structural analysis by confocal laser scanning microscopy, three distinct cell populations adjacent to odontoblasts, glial fibrillary acidic protein (GFAP)(+) seracytes, S100(+) telacytes, and HLA-II(+) alacytes were identified in peripheral human dental pulp. Subsequent molecular fingerprinting by quantitative reverse transcriptase-polymerase chain reaction established these cells as analogous to radial glia (GFAP(+) cells), astrocytes (S100(+) cells), and microglia (HLA-II(+) cells) of central nervous system organs. In the cell-rich zone of the pulp, S100(+) cells formed a network, ensheathed unmyelinated axons, and extended end-feet around the capillaries. The microcirculation adjacent to the glial cells in the cell-rich zone possessed ultrastructural features and a gene expression profile typical of the blood-brain barrier system. These novel findings support a new paradigm for understanding sensory functionality of dental pulp by the demonstration of a sophisticated neural structure in the human dental pulp that is analogous to other central sensory organs. Further, the structure that is revealed informs the concept of the evolutionary origin of the dental pulp, suggesting that a neurosensory organ was the precursor structure of teeth.