Figure 1.

Negative feedback loops and somitogenesis. (a) Negative feedback loop autoregulation. Core oscillators, often encoding transcriptional repressors, participate in negative feedback loops to sustain autoregulatory genetic oscillations. Within each gene expression cycle, segmentation clock mRNA and protein are produced in increasing amounts, and increased protein levels correspond to decreased transcriptional activation as segmentation clock protein inhibits its own expression. As segmentation clock mRNA and protein are both degraded, repression of segmentation clock gene expression is released, allowing for another cycle of expression to begin. Collectively, this forms a self-sustained negative feedback loop. (b) Species-specific segmentation clock periods. Clock periodicity varies widely across vertebrates. However, the tempo of oscillations corresponds to the timing of somite formation in all species. The examples shown are classic hairy enhancer of split orthologs, but other genes also oscillate. The tempo of oscillations is determined by species-specific biochemical rates of gene expression. (c) Oscillating PSM cells receive positional information from anterior-posterior gradients. Core segmentation clock oscillators, like zebrafish her1, are expressed in the PSM and tailbud. As cells in the tailbud proliferate, the tailbud extends and cells become displaced into the posterior PSM. Once in the posterior PSM, cells initiate robust oscillatory gene expression. These cell-autonomous oscillations appear as travelling waves across the PSM from posterior to anterior (shown in blue), and are coordinated by Notch-mediated cell-cell communication. At the determination front, which is established by opposing Fgf/Wnt and retinoic acid signaling gradients, cells transition from a presomitic to somitic cell state and a new somite boundary is formed. Although neglible over just one oscillation, PSM size changes over developmental time, gradually shrinking as the tailbud ceases to proliferate and somite formation continues. Image created using Biorender.com.