Instability of Notch1 and Delta1 mRNAs and reduced Notch activity in vertebrate neuroepithelial cells undergoing S-phase

Vertebrate neurogenesis is controlled through lateral inhibitory signals triggered by the Notch receptor and its ligand Delta. In the E4 chick embryo, the capacity of neural precursors to express the neurogenic genes Notch1 and Delta1 becomes reduced during S-phase, suggesting that their competence to trigger lateral inhibitory signals varies at different stages of the cell cycle. Here we show that the reduction of neurogenic gene expression during S-phase is extensive to later developmental stages and to other species; and it correlates with lower expression of lunatic Fringe and diminished capability to induce the expression of cHairy1/Hes1 and Hes5-1. We also show that the cell cycle-dependence of Notch1 and Delta1 expression is due to a remarkable decrease of mRNA stability during S-phase. These results provide evidence that the capacity of vertebrate neural precursors to express neurogenic genes and trigger lateral inhibitory signals is functionally coordinated with the cell cycle. © 2008 Elsevier Inc. All rights reserved.This work was supported by the Ministerio de Ciencia y Tecnología (BCM2003-03441/BFU2006-00805), Fundacion “La Caixa” (BM05-71-0), and FUNDALUCE.Peer Reviewe