HES transcriptional repressors are important components of the Notch pathway 
that regulates neurogenesis from Drosophila to vertebrates. These proteins are 
normally induced by Notch activity and inhibit neural commitment by antagonizing 
the activity of proneural genes. We describe here four chick hes genes that are 
expressed during neurogenesis: three hes5-like genes (hes5-1, hes5-2 and hes5-3) 
and one hes6-like (hes6-2). We show that hes6-2 represses transcription of the 
hes5 genes, thus functioning as a negative regulator of Notch signaling. 
Conversely, hes6-2 may be repressed by hes5 activity. In cells committing to 
differentiation, we find that hes6-2 is up-regulated by proneural genes and 
contributes to the proneural program of neuronal commitment by preventing Notch 
activity in these cells. In neural progenitors, Notch signaling produces an 
initial burst of hes5 activity, which represses hes6-2. However, as hes5 
transcription declines due to negative auto-regulation, hes6-2 may become active 
and inhibit the remaining hes5 activity to end Notch signaling. These cells can 
then enter a new cycle of fate decisions and will be kept as progenitors if a 
new pulse of Notch activity occurs. Maintenance of progenitors during vertebrate 
neurogenesis therefore requires that these cells go through successive cycles of 
Notch activity. We propose that the hes5/hes6 circuitry of negative 
cross-regulations is a conserved feature of the Notch pathway that underlies 
these cycles in neural progenitors.