Regulatory Mechanism of Neural Progenitor Cells Revealed by Optical Manipulation of Gene Expressions
Neural stem/progenitor cells are multipotent and self-renewable cells that can give generate neurons, astrocytes, and oligodendrocytes. These processes are controlled by multiple basic-helix-loop-helix (bHLH) transcription factors. bHLH transcription factors also regulate direct reprogramming of adult somatic cells into neurons and oligodendrocytes. Thus, bHLH factors play pivotal roles in development and regeneration of the nervous system. Here, we review essential functions of bHLH factors, especially focusing on the regulatory mechanism through the dynamic expression changes. To precisely analyze the functional roles of dynamic gene expression changes, tools that manipulate gene expression at fine temporal and spatial resolution are needed. We also review novel strategies to optically manipulate gene expression dynamics in neural progenitor cells.
KeywordsbHLH transcription factor Neural progenitor cells Gene expression Oscillation Optogenetics
The basic-helix-loop-helix (bHLH) transcription factors Hes1, Ascl1/Mash1 and Olig2 facilitate the fate determination of astrocytes, neurons and oligodendrocytes, respectively (Imayoshi and Kageyama 2014). However, these bHLH transcription factors are co-expressed in multipotent self-renewing neural progenitor cells even before cell fate choice (Imayoshi et al. 2013). This finding indicates that these fate determination factors are differentially expressed between self-renewing and differentiating neural progenitor cells with unique expression dynamics. Live imaging analysis with fluorescent and bioluminescent proteins is a powerful strategy for monitoring expression dynamics. Our imaging results indicate that bHLH transcription factors are expressed in an oscillatory manner by neural progenitor cells, and that one of them becomes dominant in fate choice. We propose that the multipotent state of neural progenitor cells correlates with the oscillatory expression of several bHLH transcription factors, whereas the differentiated state correlates with the sustained expression of a single bHLH transcription factor.
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