The significance of ultradian oscillations in development

Embryos develop autonomously under a predetermined schedule. While the genes involved in these processes have been characterized intensively, how such genes are expressed at the right time remains to be determined. One of the best-characterized timing mechanisms is the segmentation clock, which regulates the periodic formation of a bilateral pair of somites from the presomitic mesoderm (PSM). Somites are metameric structures that give rise to vertebrae, ribs, skeletal muscles, and subcutaneous tissues [12]. The genes encoding the basic helix–loop–helix factor Hes7 in mammals and its homologs Her1 and Her7 (Her1/7) in zebrafish are expressed in an oscillatory manner, exhibiting wave patterns in the PSM 8, 20, 34, 42. These factors are transcriptional repressors that inhibit their own expression by binding to their own promoters 9, 10, 14. By this negative feedback mechanism, their expression autonomously becomes oscillatory in species-specific periods, for example, 30 min in zebrafish, 2 hours in mice, and 5 hours in humans 10, 31, 40, 49. These ultradian rhythms (shorter periods than the circadian rhythms) regulate not only developmental time but also various other developmental processes. Here, we review the significance of ultradian oscillations in developmental time and other forms of regulation.

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