Oscillatory control of factors determining multipotency and fate in mouse neural progenitors

The team led by the research director Ryoichiro Kageyama, professor at Kyoto University and one of its group leader Dr. Hiroshi Kori at Ochanomizu University have found by time-lapse imaging that the basic-helix-loop-helix transcription factors Ascl1/Mash1, Hes1, and Olig2 are expressed in an oscillatory manner by mouse neural progenitor cells. The team also found that in each differentiation lineage, one of the factors becomes dominant.

To demonstrate the functional importance of oscillatory or sustained expression patterns of Ascl1, the team adopted the optogenetic gene expression system using the Gal4 DNA-binding domain and p65 activation domain fused with Neurospora crassa photoreceptor Vivid (GAVPO), and found that although sustained Ascl1 expression promotes neuronal fate determination, oscillatory Ascl1 expression maintains proliferating neural progenitor cells.

The paper was published in the online version of Science on Oct 31, 2013. This is a major advance in understanding the significance of the oscillatory and sustained expression of proneural factors in regulation of self-renewal and fate choice of neural stem cells.

Also, their demonstration that the light-switchable gene expression system offers a new way to control the proliferation and differentiation of stem cells by changing the light exposure pattern rather than using different growth factors or chemicals showed its applicability to the regeneration technology.