Hes genes, encoding basic helix-loop-helix (HLH) transcriptional repressors, are 
mammalian homologues of Drosophila hairy and Enhancer of split genes, both of 
which are required for normal neurogenesis in Drosophila. There are seven 
members in the human Hes family, Hes1-7, which are expressed in many tissues and 
play various roles mainly in development. All Hes proteins have three conserved 
domains: basic HLH (bHLH), Orange, and WRPW domains. The basic region binds to 
target DNA sequences, while the HLH region forms homo- and heterodimers with 
other bHLH proteins, the Orange domain is responsible for the selection of 
partners during heterodimer formation, and the WRPW domain recruits 
corepressors. Hes1, Hes5, and Hes7 are known as downstream effectors of 
canonical Notch signaling, which regulates cell differentiation via cell-cell 
interaction. Hes factors regulate many events in development by repressing the 
expression of target genes, many of which encode transcriptional activators that 
promote cell differentiation. For example, Hes1, Hes3, and Hes5 are highly 
expressed by neural stem cells, and inactivation of these genes results in 
insufficient maintenance of stem cell proliferation and prematurely promotes 
neuronal differentiation. Recently, it was shown that the expression dynamics of 
Hes1 plays crucial roles in proper developmental timings and fate-determination 
steps of embryonic stem cells and neural progenitor cells. Here, we discuss some 
key features of Hes factors in development and diseases.