The role of the transcription factor AKNA in neurogenesis: from development to reprogramming.

点击翻译按钮获取中文摘要

The mechanisms of neurogenesis are crucial not only for ontogenetic and phylogenetic brain development, but also for any attempts to replace degenerated neurons. Towards identifying novel molecular mechanisms of neurogenesis we performed genome-wide expression analysis of neurogenic versus non-neurogenic progenitors both in the developing and adult forebrain. This revealed the transcription factor Akna as a proneurogenic candidate factor given its higher expression levels in neurogenesis. Indeed, first gain- and loss-of-function experiments in the developing mouse forebrain reveal a potent neurogenic role, enhancing neurogenesis upon overexpression and retaining cells in an undifferentiated state upon knock-down. Therefore we now aim in this proposal to examine the molecular and cellular basis of these phenotypes upon Akna manipulation and determine its direct down-stream targets by genome-wide expression analysis and ChIP. In addition, we shall examine its potential role in adult neurogenesis and determine its potency in direct reprogramming by introducing it into non-neuronal cells and assaying to which extent it may be sufficient to elicit neurogenesis on its own or in combination with other factors. This will allow important insights into the molecular mechanisms of neurogenesis by unraveling novel down-stream effectors of a novel neurogenic factor.