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.
Cisneros
Elsa
E
Instituto Cajal, CSIC, Avda Dr Arce 37, E-28002 Madrid, Spain.
Latasa
Maria Jesús
MJ
García-Flores
Marta
M
Frade
José María
JM
D000818:Animals; D030161:Avian Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002642:Chick Embryo; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D046569:Neuroepithelial Cells / Q000166:cytology / Q000502:physiology*; D011247:Pregnancy; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016196:S Phase / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
D030161:Avian Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D012333:RNA, Messenger; D051881:Receptor, Notch1; C064045:delta protein