During development, somites form by periodic budding from the pre-somitic mesoderm (PSM), and give rise to the vertebral column and most of the muscles and skin. This process is driven by the pulsatile expression of ‘clock genes’, the expression of which is synchronized across the PSM. This synchronicity is regulated by the Notch pathway. Notch1 and its ligand Delta1 (Dll1) are reported to be expressed in a continuous gradient in the PSM and it is unclear how these static receptor and ligand profiles can drive and synchronise pulsatile gene expression. Through experiments in mouse and chick (p. ), Kim Dale and colleagues find that, in addition to their graded expression across the tissue, Notch1 and Dll1 mRNA and protein levels actually oscillate themselves, in a manner dependent on Notch and Wnt, respectively. Moreover, Notch1 and Dll1 waves are coordinated with the cyclical expression of Lfng, a known Notch target, and with the oscillating levels of the activated Notch intracellular domain, indicating a periodical activation of the Notch pathway. This study provides the first evidence of the pulsatile production of endogenous Notch and Delta at the protein level, and offers a potential mechanism by which cells synchronize to give rise to pulsatile waves across the PSM.
