Multiple functions of Hes genes in the proliferation and differentiation of neural stem cells.

The HES proteins (hairy and Enhancer of split (E(spl)) homologs) are basic helix-loop-helix (bHLH) transcription factors that regulate the proliferation and differentiation of stem cells. Family members HES1, 3, and 5 are all critical regulators of nervous system development. The Hes genes exhibit oscillatory expression levels, and this dynamic expression allows for the complex regulation of numerous downstream genes such as Ascl1, Neurog2, Olig2 involved in the differentiation of specific cell types. In addition, HES proteins act as hubs for the molecule crosstalk among Notch, Wnt, and other signaling pathways that regulate nervous system development.