Transplanted clonal neural stem-like cells respond to remote photic stimulation following incorporation within the suprachiasmatic nucleus

Multipotent neural stem-like cells (NSCs) obtained from one brain region and transplanted to another region appear to differentiate into neuronal and glial phenotypes indigenous to the implantation site. Whether these donor-derived cells are appropriately integrated remains unanswered. In order to test this possibility, we exploited the suprachiasmatic nucleus (SCN) of the hypothalamus, site of a known circadian clock, as a novel engraftment target. When a clone of NSCs initially derived from neonatal mouse cerebellum was transplanted into mouse embryos, the cells incorporated within the SCN over a narrow gestational window that corresponded to the conclusion of SCN neurogenesis. Immunocytochemical staining suggested that donor-derived cells in the SCN synthesized a peptide neurotransmitter (arginine vasopressin) characteristic of SCN neurons. Donor-derived SCN cells reacted to light pulses by expressing immunoreactive c-Fos protein in a pattern that is appropriate for native SCN cells. This region-specific and physiologically appropriate response to the natural stimulation of a remote sensory input implies that donor-derived and endogenous cells formed true SCN chimeras, suggesting that exogenous NSCs engrafted to ectopic locations can integrate in a meaningful fashion.