Waves of mouse Lunatic fringe expression, in four-hour cycles at two-hour intervals, precede somite boundary formation

During somitogenesis, cells are recruited to the caudal presomitic mesoderm (PSM) from the primitive streak (and later the tail bud), while somites separate from the rostral end as epithelial cubes [1]. This is a regular process, one somite forming every 2 hours in the mouse, that can be simulated by clock and wavefront models [2]. The chick basic helix-loop-helix transcription factor encoded by c-hairy1 is expressed in dynamic waves in the PSM, undergoing one cycle for each somite formed [3]. This is compatible with an underlying oscillating molecular clock. We have shown here that Lunatic fringe (L-fng) expression is indicative of it being one of the implementing outputs of this clock. Fringe genes regulate the Notch signalling pathway in boundary formation [4,5]. Of the known mouse genes, only L-fng is expressed in PSM [4,5] and it is required for somite segmentation and patterning [6,7]. We have now shown that L-fng is expressed as dynamic, repetitive and complex waves within the mouse PSM. A wave takes 4 hours to complete one cycle and terminates immediately at, and prior to, somite boundary formation. Consecutive waves are temporally but not spatially overlapping, being initiated in the caudal PSM every 2 hours, so offset by one half-cycle. Waves of expression are not associated with cell movement and do not require cell contact for propagation, so appear to reflect a cell-autonomous clock that is synchronous in all PSM cells.