Hox colinearity, somitogenesis clock and morphogen wavefront

Grodstein, McMillen and Levin (2023) describe the segmentation clock as perhaps the most studied example of waves of gene expression, one that helps establish the segmental pattern of the vertebrate axis.⁷ They trace it to the clock-and-wavefront model of Cooke and Zeeman (1976). It typically requires a global clock. Some versions, such as that of Cotterell and colleagues (2015), avoid this requirement and have an RD-like flavor. Across species the model can produce a variable number of vertebrae.⁷ Pai and colleagues (2012) note that the bilateral transcriptional waves driving the clock show consistent differences in timing between the two sides of the body.⁴

Ten Tusscher and Hogeweg (2011) summarise experimental data suggesting that initial Hox activation in the primitive streak phase is temporally colinear and may involve timing mechanisms.¹ They add that Hox activity in the presomitic mesoderm and during somite formation appears to be under more individual gene level control, coordinated with the clock and wavefront.² They contrast their evolved networks with the work of Francois and Siggia, who found that a propagating wavefront needed a special timer gene to control the order and place of gene activation.³ Ten Tusscher and Hogeweg obtained anterior-posterior differentiation without a timer gene. They used alternative attractors and a long, complex transient instead.³ In their segment-first simulations segmentation and patterning both depended on the wavefront and needed some coordination. This resemblance evolved without being selected for.²

Arendt and colleagues (2015) argue that cnidarian gastric pouches are homologous to the coelomic cavities of bilaterians. As support they report that gastric pouches and bilaterian somites share staggered, collinear hox expression. The expression boundaries coincide with the boundaries between pouches or somites.⁵ Baluška and Levin (2016) draw a different kind of parallel. They write that in the root apex transition zone cells and their membranes oscillate in almost all their activities. They say these zones resemble the presomitic mesoderm segmentation clocks that underlie vertebrate embryo segmentation.⁶

Grodstein and colleagues state that many details of the segmentation clock, including the reasons for its robustness, remain unknown, and that some clock errors do not seem to self-correct.⁸ They contrast it with their own model, whose waves perform measurement and need no clock.⁸ McMillen and Levin (2024) instead present the clock as collective intelligence that is functionally robust to interventions. They say that experiments radically altering the geometry of the tissue test its intelligence.⁹ They report that presomitic mesoderm cells do not oscillate when cultured alone but resume when cultured together. They also report that grafted cells from a different clock phase synchronize with their lateral neighbours.⁹ The two works stress different sides of the clock: unrepaired errors in one, robustness in the other.⁸⁹