The role of sonic hedgehog in adult neural progenitor cell proliferation in vitro and in vivo

Neural stem and progenitor cells have significant promise for the regeneration of tissue from the effects of trauma or neurodegenerative disorders, such as Alzheimer´s or Parkinson´s diseases. However, our understanding of the signaling factors and basic mechanisms that control their behavior must be greatly improved before this promise can be achieved. We have investigated the role of sonic hedgehog (Shh), a signaling protein vital for the development of the nervous system, in regulating adult neural stem cells from the hippocampus. We found high levels of expression of the Shh receptor, Patched, in the dentate gyrus region of adult rat brain, where hippocampal neural progenitor cells are believed to reside, as well as in neural stem cells isolated for the hippocampus. Furthermore, the addition of recombinant Shh to cells in culture elicited a strong time and dose dependent proliferative response. Finally, injection of an adeno-associated viral (AAV) vector carrying Shh cDNA into the hippocampus resulted in a 3.3 fold increase in stem cell proliferation as compared to an AAV-GFP control. This work identifies Shh as a novel regulator of adult hippocampal progenitor cell function and also, to our knowledge, demonstrates the first known role of Shh in adult organisms.