OTX2-Astroglia Map a Path Through the Human Amygdala Towards the Olfactory Bulb

Abstract

Orthodenticle homeobox 2 (OTX2) is a highly conserved homeoprotein transcription factor that performs a variety of functions throughout the lifespan. Past research establishes OTX2 as necessary in pre-natal head and eye development, post-natal opening of neural plasticity, and adult maintenance of retinal pigment epithelium (RPE) function and a mature state of perineuronal nets (PNNs). Previous work in rodents also show that OTX2 derived from the choroid plexus (ChP) is internalized within astroglia in the subventricular zone (SVZ). These cells, called OTX2-astroglia, regulate the expression of extracellular matrix (ECM) molecules for the organization of the rostral migratory stream (RMS) and the guidance of neuroblasts migrating across the RMS towards the olfactory bulb (OB). Little is known, however, about OTX2’s cellular and anatomical localization in the adult human brain. OTX2-astroglia are found in the human amygdala, suggesting that these cells may also regulate the expression of ECM molecules in the human RMS for neuroblast migration. In order to determine whether OTX2-astroglia may have a role in neuroblast migration through the regulation of ECM molecules, we sought to determine whether OTX2-astoglia form a path through the human amygdala from the SVZ to the OB using immunochemical staining and light microscopy. We collected whole human amygdala specimens (n = 6) and performed immunochemistry to identify OTX2-astroglia. We then mapped OTX2-astroglia within the human amygdala using light microscopy and finalized the maps using a graphics editor. We hypothesized that OTX2-astroglia would form a path through the human amygdala to the OB. Our data show that a path does trail from the ventral portions of the amygdala to the dorsolateral area, towards the OB. We also found another path of OTX2-astroglia trailing laterally and superiorly towards the temporal lobe. These findings suggest that OTX2-astroglia in the human amygdala may support migrating neuroblasts towards the OB. Further studies are needed to confirm whether the OTX2-astroglia are stationary or migratory and what qualities in RMS astroglia contribute to robust neuroblast migration.