A consequence of epithelialization depending on both receiving a Notch-mediated wave of gene expression (as an “okay to segment”) and becoming competent based on an Fgf8 concentration threshold means that the size and number of somites is based on two factors: the rate of segmenting oscillations and the rate of axis elongation. In fact, it is the ratio of these two rates that sets the parameters for somite number and size. For instance, let’s represent the rate of the clock as τ and the rate of axis elongation as α. If α is both sustained and in balance with τ, an infinite number of identically sized somites are theoretically possible. Alternatively, if τ is faster than α, somite formation will eventually catch up to the tailbud and terminate somitogenesis. The current model for the termination of somitogenesis is that axis elongation (α) slows, and as new somites become progressively closer to the tailbud, they bring with them the inhibitory actions of retinoic acid that arrest tailbud development (Gomez and Pourquié 2009).
Somite size could also be altered in predictable ways by manipulating these rates. Comparative analysis of somitogenesis across species has suggested that modulation of the rate of the molecular clock has been a major mechanism for adaptation of somite number. As an example, snakes can have several hundred pairs of somites, compared with the approximately 60 pairs found in the mouse and chick and the approximately 30 pairs found in zebrafish. Olivier Pourquié and colleagues compared the rates of PSM elongation and the segmentation clock exhibited by corn snake, mouse, and chick (among other species). The snake’s somites are about three times smaller than the somites of the mouse or chick (Gomez et al. 2008). Although the PSM of snakes is modestly larger than that of the chick or mouse, the most significant contribution to the greater number of smaller somites in snakes is a highly accelerated clock. Genes such as Lunatic fringe were found to show upwards of nine bands of oscillations in snakes, compared with one to three bands found in the chick and mouse (Figure 1; Gomez et al. 2008). Therefore, a greater number of Notch-mediated oscillations over the course of axis elongation will divide the PSM more times, creating more somites and more vertebrae.
Is the clock analogy sufficient? It certainly helps us understand the critical mechanisms influencing somitogenesis. Like all clock analogies, however, it makes the assumption that the rate of time stays constant. Work in the lab of Andrew Oates has demonstrated that due to the gradual change in the rate of axis elongation over time in zebrafish, the waves of oscillating segmentation genes (the period from onset to arrest) are also shortening, a phenomenon the researchers compare to the Doppler effect (Soroldoni et al. 2014). How are the different facets of somitogenesis (axis elongation, the determination front, epithelialization, and the clock) intricately coordinated to respond to change? If time is not steady, what new model can you come up with to integrate all these mechanisms?
Gomez, C., and O. Pourquié. 2009. Developmental control of segment numbers in vertebrates. J. Exp. Zool. 312B: 533–544.
Gomez, C., E. M. Ozbudak, J. Wunderlich, D. Baumann, J. Lewis, and O. Pourquié. 2008. Control of segment number in vertebrate embryos. Nature 454: 335–339.
Soroldoni, D., D. J. Jörg, L. G. Morelli, D. L. Richmond, J. Schindelin, F. Jülicher and A. C. Oates. 2014. Genetic oscillations: A Doppler effect in embryonic pattern formation. Science 345: 222–225.
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