Dynamic notch signaling in neural progenitor cells

Abstract

Notch signaling plays an essential role in maintenance of neural progenitor cells. Differentiating neurons express Notch ligands such as Delta-like1 (Dll1), which activate Notch signaling in neighboring cells. Activation of Notch signaling induces the expression of Hes1 and Hes5, which repress proneural gene expression, thereby maintaining neural progenitor cells. Thus, differentiating neurons keep their neighbors undifferentiated. Interestingly, Hes1 expression oscillates with a period of 2-3 h by negative feedback, and Hes1 oscillations drive the oscillatory expression of Dll1 and the proneural gene Neurogenin2 (Neurog2). Neurog2 oscillation cannot induce neuronal differentiation, and Dll1 oscillation leads to the mutual activation of Notch signaling between neighboring cells. Thus, neural progenitor cells also keep each other undifferentiated via oscillation in Notch signaling. Not all cells express Hes1 in an oscillatory manner: cells in boundary regions sucha the isthmus express Hes1 in a sustained manner, and this sustained Hes1 expression seems to be important for the maintenance of boundary regions. Thus, Notch signaling molecules regulate various aspects of neural development by changing the expression dynamics.