| Identifying the cellular origins of gliomas has been elusive, partly due to the lack of models in which the neurodevelopmental biology of brain tumors can be investigated. Using molecular and genetic tools a transgenic mouse model that develops high grade gliomas was studied. We hypothesized that the neurogenic subventricular zone to be the brain region from which the glioma cell of origin would arise. This area was characterized and labeled with a oligonucleotide library that allows for lineage tracing of gliomas once formed. Gliomas were comprised of heterogeneous clones, with the consistent presence of a dominant overrepresented clone. In animals with gliomas, neurogenesis is altered with loss of neuronal committed progenitor markers. This process is partly mediated by map kinases, and their inhibition leads to increased neuronal differentiation in vitro of transgenic mouse neurospheres and human glioma cells. |
