Lfng Regulates the Synchronized Oscillation of the Mouse Segmentation Clock Via Trans-repression of Notch Signalling

Overview

Journal Nat Commun

Specialty Biology

Date 2012 Oct 18

PMID 23072809

Citations 45

Authors

Yusuke Okubo

Takeshi Sugawara

Natsumi Abe-Koduka

Jun Kanno

Akatsuki Kimura

Yumiko Saga

Affiliations

Soon will be listed here.

Abstract

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.

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