Fate determinant expression in the lesioned brain: Olig2 induction and its implications for neuronal repair.
Although stem cells persist in restricted regions of the adult mammalian central nervous system (CNS), replacement of neurons does not take place in most regions in intact conditions or after injury. In the last years, proliferative multipotent cells have been isolated from the parenchyma of many CNS regions considered constitutively nonneurogenic, suggesting that the nonneurogenic CNS parenchyma is endowed with a latent neurogenic potential that might be exploited for neuronal replacement. However, neurogenic fate determinants acting during development and in the germinative zones are not expressed in the intact brain and after lesion, thus arguing against the presence of neurogenic competence in parenchymal precursors. Conversely, the basic helix-loop-helix transcription factor Olig2 is widely expressed in subsets of glia cells and progenitors, and it is strongly induced at different sites by both acute and chronic injury, albeit with different mechanisms. Antagonizing Olig2 function in cells proliferating after an acute lesion leads to the upregulation of the neurogenic determinant Pax6 and results in a significant number of newly generated immature neurons. Therefore, Olig2 acts as a repressor of neurogenesis in cells reacting to brain injury. Finding the proper way to fully derepress the neurogenic determinants in these cells, together with providing favorable environmental signals, may represent an effective approach towards evoking neuronal repair from parenchymal precursors.
Buffo
Annalisa
A
Department of Neuroscience, University of Turin, Turin, Italy. annalisa.buffo@unito.it
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D000076104:Oligodendrocyte Transcription Factor 2; D014945:Wound Healing / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C405708:OLIG2 protein, human