Lfng regulates the synchronized oscillation of the mouse segmentation clock via trans-repression of Notch signalling.
The synchronized oscillation of segmentation clock is required to generate a sharp somite boundary during somitogenesis. However, the molecular mechanism underlying this synchronization in the mouse embryos is not clarified yet. We used both experimental and theoretical approaches to address this key question. Here we show, using chimeric embryos composed of wild-type cells and Delta like 1 (Dll1)-null cells, that Dll1-mediated Notch signalling is responsible for the synchronization mechanism. By analysing Lunatic fringe (Lfng) chimeric embryos and Notch signal reporter assays using a co-culture system, we further find that Lfng represses Notch activity in neighbouring cells by modulating Dll1 function. Finally, numerical simulations confirm that the repressive effect of Lfng against Notch activities in neighbouring cells can sufficiently explain the synchronization in vivo. Collectively, we provide a new model in which Lfng has a crucial role in intercellular coupling of the segmentation clock through a trans-repression mechanism.
Department of Genetics, SOKENDAI, Yata 1111, Shizuoka 411-8540, Japan.
Yusuke
Y
Okubo
Takeshi
T
Sugawara
Natsumi
N
Abe-Koduka
Jun
J
Kanno
Akatsuki
A
Kimura
Yumiko
Y
Saga
D000818:Animals; D001683:Biological Clocks; D002135:Calcium-Binding Proteins; D003198:Computer Simulation; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D016695:Glycosyltransferases / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D038081:Organogenesis; D051881:Receptor, Notch1 / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D019170:Somites / Q000166:cytology / Q000378:metabolism*
D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D012097:Repressor Proteins; D016695:Glycosyltransferases; C498392:Lfng protein, mouse