Funktionelle Analyse des Zinkfingertranskriptionsfaktors Bcl11b während der adulten Neurogenese im Gyrus dentatus

Hippocampal structures play an important role in memory and learning. The dentate gyrus, contributing in particular to the formation of new memories, is one of only two brain regions where adult neurogenesis occurs. Adult neurogenesis is a multistep process and thightly regulated by extrinsic and intrinsic factors such as transcription factors. Previously it has been shown that the zinc finger transcription factor Bcl11b/CTIP2, expressed specifically in postmitotic granule cells of the dentate gyrus, plays an essential role during postnatal development of the hippocampus. As a consequence, Bcl11b/CTIP2 also affects learning behaviour. Furthermore expression of Bcl11b/CTIP2 continues throughout life. In this thesis it is reported that Bcl11b is not only required during postnatal development of the dentate gyrus, but also during adult neurogenesis. Adult mice harboring a forebrain-specific deletion of Bcl11b/CTIP2 exhibit a progressively smaller size of the dentate gyrus and reduced number of granule cells. It is shown that this phenotype is independent of the survival of existing neurons but due to reduced adult neurogenesis. This reduction is caused either by a decreased proliferation rate or a depletion of the stem cell compartment. In addition the forebrain-specific ablation of Bcl11b/CTIP2 results in arrested differentiation of adult born granule cells. Taken together these data strongly suggest an important role of Bcl11b/CTIP2 in adult neurogenesis