Notch signaling components such as the basic helix-loop-helix gene Hes1 are cyclically expressed by negative feedback in the presomitic mesoderm (PSM) and constitute the somite segmentation clock. Because Hes1 oscillation occurs in many cell types, this clock may regulate the timing in many biological systems. Although the Hes1 oscillator is stable in the PSM, it damps rapidly in other cells, suggesting that the oscillators in the former and the latter could be intrinsically different. Here, we have established the real-time bioluminescence imaging system of Hes1 expression and found that, although Hes1 oscillation is robust and stable in the PSM, it is unstable in the individual dissociated PSM cells, as in fibroblasts. Thus, the Hes1 oscillators in the individual PSM cells and fibroblasts are intrinsically similar, and these results, together with mathematical simulation, suggest that cell-cell communication is essential not only for synchronization but also for stabilization of cellular oscillators.Hes1 ͉ oscillation ͉ luciferase ͉ basic helix-loop-helix gene S omites, precursors for the segmental structures such as the vertebral column, ribs, and skeletal muscles, are generated in a head-to-tail order by periodic segmentation of the anterior end of the presomitic mesoderm (PSM). This periodic event is regulated by the somite segmentation clock, which is composed of Notch and Wnt signaling molecules (1-6). In the PSM, Notch components such as the basic helix-loop-helix genes Hes1 and Hes7 are cyclically expressed, and each cycle leads to segmentation of a bilateral pair of somites (7-11). This oscillatory expression occurs in a synchronous manner but with the caudalto-rostral phase delay, resulting in wave-like propagation of the expression domains from the caudal to the rostral direction. It has been shown that this oscillatory expression depends upon a negative feedback loop (12-18).Interestingly, Hes1 oscillation occurs in many cell types in addition to the PSM after serum treatment or activation of Notch signaling, suggesting that this clock may regulate the timing in many biological systems (12). Although Hes1 oscillation is stable in the PSM, it is damped after three to six cycles in other cells, raising the possibility that the Hes1 oscillator of the PSM cells is intrinsically different from that of other cell types (8, 12). However, the damping could result not only from damped oscillation in each cell but also from desynchronization between cells, and it is not clear which is the case. It was shown that PSM cells could become desynchronized when they are dissociated (19), but the nature of the segmentation clock in individual PSM cells remains to be determined.To understand the dynamics of the somite segmentation clock, we attempted real-time imaging of Hes1 expression in the PSM and the dissociated individual PSM cells. Here, we found that Hes1 oscillation is stable (both the period and amplitude are relatively constant) in the PSM but unstable (the period and amplitude are variable) in the individu...

Serum response has been used as a model for studying signaling transduction for many biological events such as cell proliferation and survival. Although expression of many genes is up-or downregulated after serum stimulation, the Notch effector Hes1 displays oscillatory response. However, the precise mechanism and biological significance of this oscillation remain to be determined. Socs ͉ microarray analysis ͉ mathematical simulation

Living organisms process information without any central control unit and without any ruling clock. We have been studying a novel computational strategy that uses a geometrically arranged excitable field, i.e., "field computation." As an extension of this research, in the present article we report the construction of a "direction detector" on an excitable field. Using a numerical simulation, we show that the direction of a input source signal can be detected by applying the characteristic as a "coincidence detector" embedded on an excitable field. In addition, we show that this direction detection actually works in an experiment using an excitable chemical system. These results are discussed in relation to the future development of "field computation."PACS numbers: 05.45.-a, 05.70.Ln